Synthesis of Functionalized Thioxanthones, Indenones ...

Synthesis of Functionalized Thioxanthones, Indenones, Indoles, and

Anthraquinones by Regioselective Palladium (0)-Catalyzed Cross-

Coupling Reactions

Dissertation

zur

Erlangung des Doktorgrades

doctor rerum naturalium (Dr. rer. nat.)

der Mathematisch-Naturwissenschaftlichen Fakultät

der Universität Rostock

vorgelegt von

Dhafer Saber Khalaf Zinad geb. am 28 August 1978, Mosul, IRAQ

Rostock, January 2012

urn:nbn:de:gbv:28-diss2012-0017-1

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Die vorliegende Arbeit entstand in der Zeit von July 2009 bis August 2011 am

Institut für Chemie der Universität Rostock

Erinreichung der Dissertation:

1- Dekan: Prof. Dr. Christoph Schick, Mathematisch-Naturwissenschaftliche Fakultät,

Universtät Rostock.

2- Gutachter: Prof. Dr. A. Stephen K. Hashmi, Organisch-Chemisches Institut, Fakultät

für Chemie und Geowissenschaften, Ruprech-karls-Universtät Heidelberg.

3- Gutachter: Prof. Dr. Peter Langer, Institut für Chemie, Mathematisch-

Naturwissenschaftliche Fakultät, Univestät Rostock.

Tag der Abgabe: October, 2011

Prüfer Hauptfach: Prof. Dr. Peter Langer

Wissenschaftliches Kolloquium: 31. 01. 2012�

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Dedication

To The Spirit of my Beloved Father …

Will not forget you …

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Acknowledgment

First of all, I am thankful to the Merciful, Omniscient Almighty ALLAH with his help and

blessing always.

I would like to express my deep thanking to all who added to the successful completion of my

PhD.

Special thanks and appreciation to Prof. Dr. Dr. h.c. Peter Langer for his guidance and

support.I always found him ready to facilitate my research by effective discussions. I feel honor

to express my sincere thanks to him.

Many thanks to Prof. Dr. Hartmut Laatsch due to his exceptional support during my research in

the Institute of Organic and Bimolecular Chemistry in Göttingen University.

I would like also to express my thanks to Dr.Holger Feist for his valuable guidance. I am also

thankful to Dr.Martin Hein, Dr.Dirk Michalik, Dr.Alexander Villinger and all the technical

members in NMR, IR, MS, X-ray laboratories in the institute of chemistry in Rostock university

for their help and continuously support .

Thanks a lot to Dr.Munawer Hussain for his nice contribution and useful cooperation.

I feel grateful to my lab colleagues especially Friedrich Erben for his nice lab fellow and

providing me nice atmosphere in the lab.

Many thanks to Prof. Dr.Layla Abdulla Mustafa, Ibrahim, Raeed, Anwer, Ahmed Nafe,

Ghazwan, Ahmed Salem, Omer, Nadi, Verena Wolf, Nawaz, Iftikhar, Hung, Marcello and all of

my colleagues and teachers in Mosul University in Iraq.

I would like to thank DAAD Foundation for providing me the financial supports during my PhD.

many thanks to Mrs.Margret Steuernagel, Mrs.Sandra Wojciechowsky for their dedication to

support and facilitate me in all related problems.

Thanks a lot and appreciation to Prof. Dr. Salah Al-abbasi the Iraqi Cultural Attache in Berlin

for his continuous support.

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Finally, I would like to express my heartiest gratitude and respect to my great parents for their

love, support, salutary advices and emboldening attitude that kept my spirit alive.

Thanks a lot to all members of my family. My brothers and sisters: Dr.Yasser, Asmaa, Huda,

Dr.Hany, Omar, Younis…Thank you all for your support and encouragement. I am grateful to all

of you. May ALLAH give me the courage, strength and opportunity that I can support every one

of you.

Special thanks to my wonderful wife (Huda) and my nice Son (Zaid) who they suffered with me a

lot during my hard time with chemistry. Without them I am unable to find myself and the life will

be without meaning.

I owe to all of you in my life!

Dhafer Saber

University of Rostock

Germany, 2011

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Table of Contents

Summary……………………………………………………………………………… 3-8

1. Introduction…………………………………………………………………………… 9

1.1 General Introduction…………………………………………………………….... 9

1.2 Characteristic Features of Palladium-Catalyzed Cross-Coupling Reactions…….. 9-10

1.3 Palladium-Catalyzed Cross-Coupling Reactions……………………….. ………. 9-10

1.4 Fundamental Reactions of Palladium Compounds……………………………...... 11-12

1.5 Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions……………… 13-16

1.6 Palladium-Catalyzed Heck Cross-Coupling Reactions…………………………... 17-19

2. Synthesis of Functionalized Dihydroxy-9H-thioxanthene-9-ones…………………….. 20

2.1 General Introduction…………………………………………………………….... 20-21

2.2 Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of the Bis(triflates) of 1,3-

Dihydroxy- 9H-thioxanthene-9-ones…………………………………………………….... 22

2.3 Conclusion………………………………………………………………………… 26

2.4 Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of the Bis(triflates) of 1,4-

Dihydroxy-9H-thioxanthene-9-ones……………………………………………………... 29

2.5 Conclusion………………………………………………………………………… 35

3. Site-Selective Synthesis of Arylated-1H-inden-1-ones by Suzuki-Miyaura Cross-

Coupling Reactions of 2,3,5-Tribromo-1H-inden-1-one…………………………….. 36

3.1 General Introduction…………………………………………………………… 36-45

3.2 Conclusion……………………………………………………………………… 46

4. Synthesis of Arylated-1-Methyl-1H-indoles by Suzuki-Miyaura Cross-Coupling

Reactions of 2,3,6-Tribromo-1-methyl-1H-indole……………………………………. 47

4.1 General Introduction……………………………………………………………. 47-55

4.2 Conclusion……………………………………………………………………… 56

5. Synthesis of Functionalized Anthraquinones by Domino Twofold Heck-6�-

Electrocyclization Reactions of 2,3-Dibromonaphthaquinone……………………….. 57

5.1 General Introduction……………………………………………………………. 57

5.2 Conclusion…………………………………………………………………......... 61

6. Abstract……………………………………………………………………………….. 62-63

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7. Experimental Section………………………………………………………………… 64

7.1 General: Equipment, Chemicals and Work Technique……………………….. 64-65

7.2 General Procedures……………………………………………………………. 66-129

References…………………………………………………………………………. 130-136

Data for X-ray Crystal Structures………………………………………………… 137-146

Declaration / Erklärung……………………………………………………………. 147

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Abbreviations

Ar Aryl

APT Attached Proton Test

calcd Calculated

DEPT Distortion-less Enhancement by polarization Transfer

EI Electron Impact

ESI Electrospray Ionization

EtOAc Ethyl Acetate

Hz Hertz

HRMS High Resolution Mass Spectrometry

IR Infrared Spectroscopy

MS Mass Spectrometry

Mp Melting Point

Ph Phenyl

NBS N-bromosuccinimide

NEt3 Triethylamine

NMR Nuclear Magnetic Resonance

HMBC Hetronuclear Multiple Bond Correlation

NOESY Nuclear Overhauser and Exchange Spectroscopy

Tf2O Trifluoromethanesulfonic Anhydride

THF Tetrahydrofurane

TLC Thin Layer Chromatography

TMS Trimethylsilane

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Summary

The task of my thesis was to study palladium(0)-catalyzed cross-coupling reactions (Suzuki

and Heck reaction). Different types of bis(triflates) and dibromides of different substrates

(thioxanthons, indenones, indoles, naphthaquinones) were studied.

1,3- Dihydroxythioxanthones and 1,4-dihydroxythioxanthones as substrates were synthesized

in the laboratory from available chemicals and known procedures.

The palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reaction of bis(triflates) of 1,3-

dihydroxythioxanthones afforded 1,3-diarylthioxanthones. The reactions proceeded with very

good yield and excellent site-selectivity. The first attack takes place at carbon atom C-3. In

general, the site-selectivity of palladium(0)-catalyzed reactions is controlled by electronic and

steric effects. The oxidative addition of palladium usually occurs first at the most electron

deficient and sterically less hindered position. The regioselectivity of the formation of mono-

adducts for bis(triflates) of 1,3-dihydroxythioxanthone is due to the fact that carbon atom C-3 is

sterically less hindered than carbon atom C-1. Therefore, the first attack occurred at this position.

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The Suzuki-Miyaura cross-coupling reactions of bis(triflates) of 1,4-dihydroxythioxanthones

afforded 1,4-diarylthioxanthones. The reaction again proceeded with excellent site-selectivity in

favour of carbon atom C-1 which is more electron-deficient than carbon atom C-4. The attack at

carbon atom C-4 is hindered by the lone pairs of the sulfur atom. Therefore, the first attack takes

place at position 1.

Various 1,3- and 1,4-diarylthioxanthones with different electron-donating and withdrawing

groups were prepared in high yields and excellent site-selectivity. Pd(PPh3)4 was used as an

optimal catalyst for the synthesis (5 mol% per cross-coupling reaction).

2,3,5-Tribromoinden-1-one was prepared from commercially available 5-bromoinden-1-one.

The Suzuki-Miyaura reaction of this substrate was studied also in my thesis. The site-selective

Suzuki-Miyaura cross-coupling reaction of 2,3,5-tribromoinden-1-one with one equivalent of

different arylboronic acids, having both electron-donating and withdrawing groups, afforded 3-

aryl-2,5-dibromo-1H-inden-1-one in high yields and excellent site-selectivity. Pd(PPh3)4 (3

mol%) was used for this coupling reaction as a catalyst. The first attack occurred at carbon atom

C-3.

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The palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reactions to give di- and

triarylinden-1-ones proceeded with high yields and very good site-selectivity. The second attack

takes place in favour of carbon atom C-2 of tribromominden-1-one. The site-selectivity can be

explained by the fact that carbon atom C-3 is considerablly more electron-deficient than

positions 2 and 5. Carbon atom C-2 is sterically more hindered than C-5 and electronically less

deficient.

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The site-selectivity in favour of position 5 might be explained by chelation of the catalyst to

the carbonyl oxygen atom which may enhance the rate in favour of position 2.

The Suzuki-Miyaura cross-coupling reaction of 2,3,6-tribromo-1-methyl-1H-indole with

different arylboronic acids, both electron-donating and withdrawing groups, were studied also in

my thesis.

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2-Aryl-3,6-dibromo-1-methyl-1H-indoles were synthesized in high yields and excellent site-

selectivity for both electron-donating and withdrawing groups of the arylboronic acids used.

Pd(PPh3)4 (3 mol%), a solvent mixture of toluene/1,4-dioxane (4:1), and K3PO4(1.5 equiv.) as the

base were most suitable conditions for this reaction. Both symmetrical and unsymmetrical di-

and triaryl-1-methyl-1H-indoles were prepared in this project in high yields and very good site-

selectivities for both electron-donating and withdrawing groups.

The first attack occurred at carbon atom C-2 and the site-selectivity of 2,3,6-tribromo-1-

methyl-1H-indole was explained by the fact that position 2 is considerably more electron-

deficient than positions 3 and 6. Carbon atom C-6 is sterically less-hindered than C-3, therefore

the second attack occurred at C-6. The synthesis of 2,3,6-triaryl-1-methyl-1H-indoles, containing

different aryl groups, was proceeded as a one-pot synthesis with sequential addition of the

reagents. Other products were synthesized after isolation of the product of the first coupling

reaction from the first step and its reaction with a second boronic acid in a second cross-coupling

reaction.

The synthesis of functionalized anthraquinones by domino twofold 6�-electrocyclization

reactions of 2,3-dibromonaphthaquinone was studied also in my thesis. The Heck reaction of 2,3-

dibromonaphthaquinone with different types of alkenes (acrylate and styrene), having both

electron-donating and withdrawing groups, afforded substituted anthraquinones. The temperature

played an important effect in this reaction. The yields significantly decreased when the

temperature was increased. A clean reaction was observed when the reaction was carried out at

90°C. Pd(OAc)2 (5 mol%) and Buchwald ligand XPhos (10 mol%) were used for the reaction.

The products, which are not readily available by other methods, were formed in only one step

under relatively mild conditions.

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1. Introduction

1.1 General Introduction Carbon-carbon bond forming reactions played an enormously decisive and important role in

shaping chemical synthesis of organic compounds. Classical reactions, for example aldol and

Grignard-type reactions, the Diels-Alder, Wittig and related reactions, allow chemists to

construct increasingly complex carbon frameworks and thus enabled the synthesis of a myriad of

organic compounds.

During the second half of the 20th century, transition metals started to play an important role

in organic chemistry and this has led to the development of a large number of transition metal-

catalyzed reactions for creating organic molecules. Transition metals have a unique ability to

activate various organic compounds and through this activation they can catalyze the formation

of new bonds. In 2005, the Nobel Prize in chemistry was awarded to metal-catalyzed reactions

for the formation of carbon-carbon double bonds. In 2010, the Nobel Prize in chemistry is

awarded to the formation of carbon-carbon single bonds through palladium-catalyzed cross-

coupling reactions1.

1.2 Characteristic Features of Palladium-Catalyzed Reactions There are several features which make reactions involving palladium-catalysts and reagents

particularly useful and versatile among many transition metals used for organic synthesis. Most

importantly, Pd catalysts offer an abundance of possibilities of carbon-carbon bond formation.

No other transition metal can offer such versatile methods for carbon-carbon bond formations as

Pd. Tolerance of Pd-catalysts and reagents to many functional groups, such as carbonyl and

hydroxyl groups, is the second important feature. Pd-catalyzed cross-coupling reactions can be

carried out without protection of these functional groups. However, reactions involving Pd

should be carried out carefully as Pd(0)-reagents and catalysts are sensitive to oxygen and

moisture. It is sufficient to apply precautions to avoid oxidation of coordinated phosphines and

Pd(0). 2

Palladium is a noble and expensive metal. The toxicity of Pd has posed no serious problems

so far. Numbers of industrial processes, particularly for the production of fine chemicals based

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on Pd-catalyzed reactions, have been developed and are currently being operated and reflect the

advantages of using Pd catalysts commercially 3.

1.3 Palladium-Catalyzed Cross-Coupling Reactions

Based on transition-metal catalysis, the newly acquired ability to form carbon-carbon bonds

between functionalized and sensitive substrates provided new opportunities, particularly in total

synthesis, but also in medicinal and process chemistry as well as in chemical biology and

nanotechnology. Various types of palladium-catalyzed cross-coupling reactions are known in

organic synthesis, such as Heck, Stille, Suzuki, Sonogashira, Tsuji-Trost, and the Negishi

reactions (Figure 1). The increasing popularity of these reactions in synthesis is seen in every

issue of modern scientific journals dedicated to organic synthesis or organometallic chemistry

and catalysis4.

Figure 1: Types of palladium-catalyzed cross-coupling reactions (picture taken from

Angew.Chem. Ind. Ed. 2005, 44, 4442).

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With regard to the application in industry, the shown coupling reactions offer the opportunity

of shorter and more selective routes for a number of fine chemicals as compared to traditional

stoichiometric organic transformations. Thus, it is not surprising that, since the early 1990s, more

and more palladium-catalyzed reactions are transferred from academic protocols to industrial

scale. Therefore, during the last decade, the development of new catalysts which are more

productive and more active continues to be a major goal of organometallic chemistry and

homogeneous catalysis5.

1.4 Fundamental Reactions of Palladium Compounds The reaction mechanism and the synthetic applications of Pd-catalyzed cross-coupling

reactions proceed according to the following major steps6,7(Figure 2).

1. Oxidative Addition: The ‘oxidative’ addition is the addition of a molecule X-Y to Pd(0) with

cleavage of its covalent bond, forming two new bonds. Since the two previously non-bonding

electrons of Pd are involved in bonding, the Pd increases its formal oxidation state by two units,

namely, Pd(0) is oxidized to Pd(II).

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2. Insertion: The term ‘insertion’ is somewhat misleading. The insertion should be understood

as the migration of the adjacent ligand from the Pd to the Pd-bound unsaturated ligand. The

reaction below is called ‘insertion’ of an alkene to a (Ar-Pd-X) bond mainly by inorganic

chemists. Some organic chemists prefer to use the term ‘carbo-palladation’ of alkenes.

3. Transmetallation: Organometallic compounds M-R and hydrides M-H of main group

metals (M= Mg, Zn, B, Al, Sn, Si, Hg) react with Pd complexes (Ar-Pd-X) formed by

oxidative addition, and the organic group or hydride is transferred to Pd by substituting X

with R or H. In other words, alkylation of Pd or hydride formation takes place and this

process is called transmetallation.

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4. Reductive Elimination: it is a uni-molecular decomposition pathway, and the reverse of

oxidative addition. Reductive elimination (or reductive coupling) involves loss of two

ligands of cis configuration from the Pd center, and their combination gives rise to a single

elimination product as it has been shown below. By reductive elimination, both the

coordination number and the formal oxidation state of Pd(II) are reduced by two units to

generate Pd(0), and hence the reaction is named ‘reductive’ elimination. The regenerated

Pd(0) species undergo oxidative addition again. In this way, a catalytic cycle is completed

by a reductive elimination step8.

Figure 2: General mechanism for palladium-catalyzed cross-coupling reactions (picture taken

from Molecules, 2011, 16, 951-969).

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1.5 Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction The Suzuki-Miyaura cross-coupling reaction represents an extremely useful method for

the synthesis of biaryls and is widely applied in organic chemistry. The reaction involves,

for example, the palladium-catalyzed cross-coupling between organoboron compounds and aryl

halides. The scope of the reaction is not restricted to aryl derivatives, but includes also alkyl,

alkenyl and alkynyl compounds. The reaction also works well with triflates (the OH group is

converted into OTf by triflic anhydride); thus, phenolic compounds can be arylated by this

method. Boronic esters, boranes or boronic acids can be used 9. Since its discovery, the Suzuki-

Miyaura cross-coupling reaction has seen significant advancement and became one of the most

powerful carbon-carbon bond forming methods in organic synthesis. The Suzuki reaction

represents one of the, if not the most, widely used methods for aryl-aryl bond formation in

modern organic synthesis. Biaryl systems have a lot of advantages in many scientific and

economic fields, from natural products to ligands for asymmetric catalysis, pharmaceutical

compounds, and nanomaterials. Extensive research efforts have recently been extended to

develop further the utility and efficiency of the Suzuki reaction within this context10.

The reaction has important advantages including functional group compatibility, low toxicity

of reagents and intermediates, easy availability of boron derivatives, high thermal stability and

tolerance toward oxygen and aqueous solvents11.

Recently, organic chemists have turned their work to the application of this reaction for the

synthesis of more complex molecules, by using successive Suzuki-Miyaura cross-coupling

reactions with substrates containing two or more possible reactive sites12.

The mechanism usually involves three steps (Figure 3). In the first step of the reaction, the

oxidative addition of organic halides or triflates to the Pd(0) complex to form an organo-

palladium halide (R1-Pd (II)-X) takes place. This step is then followed by transmetallation with a

boronic acid derivative to give a diorgano-palladium complex (R1-Pd-R2). In the final step of the

reaction, this complex undergoes a reductive elimination resulting in the formation of a carbon-

carbon bond and regeneration of the catalyst13.

Many factors are affecting both the oxidative addition and transmetallation steps and then

affect the rate of Suzuki reactions. For example, the reactivity of the reacting substrates has an

important role to play on the oxidative addition step. Generally, the reactivity of various

substrates in Suzuki reactions is observed in the following order, Ar-I > Ar-Br > Ar-OTf > Ar-

Cl. The base supports the transmetallation step of the Suzuki reaction. Different types of bases

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are used in this reaction, e.g. potassium carbonate, potassium phosphate and cesium carbonate,

which enhances the rate of the transmetalation by increasing the nucleophilicity of the organo-

boran compound by formation of an organo-borate containing a tetravalent boron atom14.

Figure 3: Catalytic cycle of the Suzuki reaction

The Suzuki-Miyaura cross-coupling reaction is the only one among metal-catalyzed cross-

coupling reactions which can be run in biphasic (organic/ aqueous) or aqueous environments in

addition to organic solvents15.

Organo-boron derivatives can tolerate a broad range of functional groups, such as organic

halides, carbonyls, etc. The electronegativity of boron is about 2.0 which is close to the value of

carbon of 2.5 and is higher than the electronegativities of lithium, magnesium, or most of the

transition metals which range from 0.86 to 1.75. Therefore, the boronic compounds are air-stable

and also water tolerant. The starting materials and borate by-products are not toxic16.

In organic synthesis, two kinds of palladium compounds, namely Pd(II) salts and Pd(0)

complexes are used. Pd(II) compounds are mainly used as oxidizing reagents, or as catalysts for

some reactions. Pd(0) complexes are often used as catalysts. Pd(II) compounds such as PdCl2 and

Pd(OAc)2 are stable and commercially available. They can be used in two ways: as unique

stoichiometric oxidizing agents and as precursors of Pd(0) complexes. Pd(OAc)2 is commercially

available, stable and soluble in organic solvents. Commercially available Pd(OAc)2,

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PdCl2(PPh3)2, Pd(PPh3)4, Pd2(dba)3 are generally used as precursors of Pd(0) catalysts with or

without addition of phosphine ligands. Pd(PPh3)4 is a light-sensitive, air unstable, yellowish

green catalyst and a coordinatively saturated Pd(0) complex which is widely used as a catalyst

for palladium-catalyzed cross-coupling reactions17.

As these catalysts serve as a source of electrons in the reaction; the electron-rich ligands are

often the key for a successful reaction. Sterically hindered and electron-rich phosphines serve the

purpose in a best way. Many chemists all over the world are trying to synthesize most useful

ligands which can be employed to achieve the best results in the field of palladium-catalyzed

chemistry. Buchwald and co-workers18 recently have developed electron-rich, bulky biphenyl

phosphine ligands, such as S-Phos, X-Phos, and others.

Langer and coworkers extensively studied site-selective Suzuki-Miyaura cross-coupling

reactions of poly-halogenated hetero-aromatic and aromatic compounds or their triflates. In this

context, regioselective Suzuki-Miyaura cross-coupling reactions of 2,3-dibromo-1H-inden-1-

one (a), 2,3-dibromobenzofuran (b), 2,3-dibromo-1-methyl-1H-indole (c), 2,3,4-

tribromothiophene (d), 2,3,5-tribromothiophene (e), 3,4,5-tribromo-1-methyl-1H-pyrazole (f),

perchloropyrimidine (g) and perbromofuran (h) were reported (Figure 4) 19a-h.

Figure 4: Site-selective Suzuki cross-coupling reactions of various halides studied in

Langer’s group

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Site-selective Suzuki-Miyaura cross-coupling reactions of bis(triflate) substrates and

subsequently the site-selectivity of the reaction were studied as well (Figure 5). The use of aryl

triflates instead of aryl halides is particularly important in organic synthesis because it can

provide a way of forming a carbon-carbon bond at a phenolic site, which is often useful when

appropriate halides are unavailable.20

Langer’s group also reported the regioselective synthesis by Suzuki-Miyaura cross-coupling

reactions of different hydroxylated substrates, e. g. (3,4-dihydroxyphenyl)(phenyl)methanone (i)

2-((4-hydroxyphenyl)sulfonyl)phenol (j) 1,2-dihydroxyanthracene-9,10-dione (k) phenyl 1,4-

dihydroxy-2-naphthoate (l) 7,8-dihydroxy-2-phenyl-4H-chromen-4-one (m), 1,2,3,4-tetrahydro-

9,10-dihydroxyanthracen-1-one (n) 5,10-dihydroxy-11H-benzo[b]fluoren-11-one (o).21a-g

All mentioned substrates proceeded with very good yields and excellent site-selectivity.

Figure 5: Site-selective Suzuki cross-coupling reactions of dihydroxylated substrates studied in

Langer’s group

In general, complex compounds can be prepared by successive Suzuki-Miyaura cross-

coupling reactions of substrates containing one, two or more possible reactive sites. The

regioselectivity can be explained by electronic and steric parameters. The first attack usually

occurs at the more electrons deficient and sterically less hindered position22.

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1.6 Palladium-Catalyzed Heck Cross-Coupling Reaction

The Mizoroki–Heck reaction is the palladium-catalyzed C-C coupling reaction between aryl

halides or vinyl halides with activated alkenes in the presence of Pd(0) catalyst and a base. Pd(II)

acetate or Pd(II) chloride in combination with different ligands, such as triphenyl

phosphine(PPh3), S-Phos, X-Phos, tricyclohexylphosphine (PCy3) were used as catalysts to give

the corresponding substituted alkenes23.

In general, the reaction proceeds with high stereo- and regioselectivity. The reaction was

discovered independently by Heck and Mizoroki in the early 1970s. After further development in

the 1980s and 1990s, the synthesis community benefited enormously from the Heck reaction,

especially for the synthesis of pharmaceuticals and agrochemicals24. The intramolecular Heck

reaction has been well-established as a powerful tool for the construction of complex polycyclic

ring systems in the context of natural product synthesis.

In Heck reactions, the reactivity depends on the substituted olefins: more substituted olefins

resulted in a slower reaction. However, electron-poor olefins provided higher yields (electron-

withdrawing groups such as ester, ether, carboxylic acid, nitriles, located at the olefin). The type

of leaving group also plays an important role. The reactivity order is I > Br > Cl.

The generally accepted reaction mechanism is shown in Figure 6. The reaction begins with

the oxidative addition of the aryl-X compound (X = I, Br, Cl, OTf, OTs, etc) to an active ligated

Pd(0) center to form the respective Pd(II) species.

Subsequent coordination and then insertion of the alkene at the Pd(II) center generates an

alkyl palladium complex. After rotation of the carbon–carbon bond, hydride elimination takes

place and the substituted alkene is released as the terminal product. Finally, the active Pd(0)

catalyst is regenerated with base.

Besides the typical intermolecular reactions of aryl halides with ethylene, styrenes, acrylates,

enol ethers, etc., intramolecular variants exist, which form unsaturated carba- or heterocycles.

Furthermore, the Heck reaction has proven to be very useful as part of novel domino reactions25.

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Figure 6: general reaction mechanism of Heck cross-coupling reaction (picture taken from

Angew.Chem. Int. Ed. 2010, 49, 9047-9050).

The combination of the Heck cross-coupling reaction with electrocyclization reactions

provides a convenient access to a variety of carbacyclic frameworks. Pioneering work in this

field was reported by de Meijere and co-workers. Benzene derivatives have been prepared by

double Heck reactions of aliphatic 1,2-dibromoalkenes to give hexatrienes and subsequent

thermal-6π-electrocyclization of the latter. The electrocyclization can proceed smoothly, if the

central double bond of the triene system is not involved in a stable aromatic 6π-system26.

Langer’s group later studied the application of this concept to various halogenated compounds,

e.g. twofold Heck cross coupling reactions of 2,3-dibromoindenone (a) 2,3dibromo-N-

methylindole (b) 2,3-dibromobenzothiophene(c), 2,3-dibromofuran (d) 2,3dibromothiophene (e)

2,3-dibromobenzofuran (f) (Figure 7) 27a-e.

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Figure 7: Heck reaction of vicinal dibromide studied in Langer’s Group

In conclusion, the Pd(0)-catalyzed Heck cross-coupling reaction of dibrominated substrates

can provide a cyclization and aromatization by a subsequent electrocyclization. The synthesis of

the products following this type of reaction can be achieved in only one-step under relatively

mild conditions.

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2. Synthesis of Functionalized Dihydroxy-9H-thioxanthen-9-ones.2.1 General Introduction:

The first part of my work was concerned to the synthesis of functionalized thioxanthones

based on site-selective Suzuki-Miyaura cross-coupling reactions. In the literature, it has been

reported that thioxanthones show a variety of properties. These types of compounds have

considerable pharmacological relevance and occur in various natural products28. Thioxanthone

derivatives have been studied extensively owing to their medicinal properties, such as

antihistaminic, antiparasitic, neuroleptic, and antitumor activities29-33. Lucanthone and

hycanthone, a metabolite, represent bioactive natural products with thioxanthone core structure34.

A series of hycanthone derivatives have been recently reported to display high levels of in vivo

activity against murine pancreatic adenocarcinoma35-37. Thioxanthone-dioxide is also known to

exhibit significant pharmacological activities, including antitumor, cytotoxic and monoamine

oxidase (MAO) inhibitory activity38. A number of plants such as cartoxylum cochinchinense

(Lour.), contain thioxanthone derived natural products and have been used as traditional

medicines to treat fever, coughing, diarrhoea, itching, ulcers and abdominal complaints39. The

thioxanthone class of drugs are effective in the systematic treatment of psychoses; they are most

appropriately used in the therapy of schizophrenia, organic psychoses and other idiopathic

psychotic illness. These drugs have other clinically useful properties including anti-emetic, anti-

nausea, anti-histamine and the ability to potentiate the analgesics sedatives and general

anaesthetic action40. Thioxanthones are also important in the field of material sciences. Various

derivatives of thioxanthones are used as activators in the photo polymerization of ethylene-

derived unsaturated monomers (particularly acrylate derivatives)41. Moreover, alkyl-, alkoxy-

and hydroxy-substituted thioxanthones are particularly useful as heat and ultraviolet stabilizers

of polyolefins42.

Several methods were used for the synthesis of thioxanthones39,43. A rather general procedure

is based on the condensation of substituted potassium 2-chlorobenzoates with thiophenols or on

the condensation of substituted thiosalicylic acids with benzene derivatives to give 2-

phenylmercaptobenzoic acids which are subsequently cyclized by reaction with sulphuric acid, 44,45, AlCl330,33 or polyphosphoric acid (PPA)32. However, these classical methods have some

disadvantages, such as low yields, long reaction times, use of large amounts of concentrated

sulphuric acid, and lack of regiochemical control in the ring closure step. Moreover, some of

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these methods require several synthetic steps, because the starting materials are not readily

available, and are limited to activated benzoic acids and benzene derivatives containing electron-

withdrawing groups.

1,3-Dihydroxy-9H-thioxanthen-9-one was prepared, following a known procedure,46 by AlCl3

mediated reaction of thiosalicylic acid with 1,3,5-trihydroxybenzene.

1,4-Dihydroxy-9H-thioxanthen-9-one was synthesized by cyclization of 2-[(2,5-di-

hydroxyphenyl)sulfanyl]benzoic acid. The latter was prepared from benzoquinone and

thiosalicylic acid in acetic acid or other solvents (such as diethyl ether or ethanol) at room

temperature and the reaction occurs as a 1,4-addition of the nucleophile at the conjugated

bond system of the quinone with participation of one carbonyl group (which is typical of

quinones), followed by rearrangement of the adduct to produce dihydroxy-substituted

biphenyl sulfide 47.

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2.2 Site-Selective Suzuki–Miyaura Cross-Coupling Reactions of the Bis(triflates) of 1,3-Dihydroxy-9H-thioxanthen-9-one.

Results and discussion:

1,3-Dihydroxy-9H-thioxanthen-9-one 1 was prepared following a known procedure 46. The

hydroxyl group can be transformed to triflates by treatment with triflic anhydride in the presence

of pyridine as a base. The triflic anhydride was added at -78oC and the mixture was allowed to

warm to room temperature. Based on the above mentioned procedure, compound 1 was

converted to the bis(triflate) 2 which was isolated as a yellow solid in 80% yield (Scheme1).

Scheme 1: Synthesis of 2. Reagents and conditions: i, CH2Cl2, 1 (1.0 equiv.), Et3N (4.0 equiv.),

Tf2O (2.4 equiv.), -78°C � 20°C, 8 h.

The Suzuki–Miyaura cross-coupling reaction of 2 with arylboronic acids 3a–g (2.4 equiv.)

afforded the 1,3-diarylthioxanthones 4a–g (Scheme 2, Table 1). The structures of all products

were confirmed by spectroscopic methods. Very good yields were obtained both for reactions of

electron-rich and poor arylboronic acids. The best yields were obtained when the reactions were

carried out using Pd(PPh3)4 (10 mol%) as catalyst, K3PO4 (3.0 equiv.) as base and when the

reaction was carried out using 1,4-dioxane as a solvent at 90°C for 8 h.

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Scheme 2: Synthesis of 4a-g. Reagents and conditions: i, 2 (1.0 equiv.), 3a-g (2.4 equiv.),

Pd(PPh3)4 (10 mol%), K3PO4 (3.0 equiv.), 1,4-dioxane, 90°C, 8 h.

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Table 1: Synthesis of 4a-g

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a Yields of isolated products.

The Suzuki–Miyaura reaction of 2 with arylboronic acids 3b,c,d,f,g,h,i,j (1.1 equiv.) resulted

in the formation of the 3-aryl-1-(trifluorosulfonyloxy)-thioxanthones 5a-h in a good yields and

excellent site-selectivity (Scheme 3, Table 2).��

Scheme 3: Synthesis of 5a-h and of 6a-c. Reagents and conditions: i, 2 (1.0 equiv.),

3b,c,d,f,g,h,i,j (1.1 equiv.), Pd(PPh3)4 (5 mol%), K3PO4 � �� !"��#�$%�ii, 5b,c,f

(1.0 equiv.), 3a,h,k (1.1 equiv.), Pd(PPh3)4 (5 mol%), K3PO4 (1.5 equiv.), 1,4-dioxane, 90°C, 6 h

3 4 Ar 4(%)a

a a 2-(MeO)C6H4 90

b b 4-EtC6H4 81

c c 4-tBuC6H4 86

d d 3,5-Me2C6H3 77

e e 4-MeC6H4 84

f f 4-ClC6H4 70

g g 3-(CF3)C6H4 75

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Table 2: Synthesis of 5a-g and 6a-c


It was proved to be important to carry out the reaction at 60 instead of 90°C in order to induce

a good site-selectivity and to avoid double attack. Good yields were again obtained both for

reactions of electron rich and poor arylboronic acids. The structure of compound 5b (Figure 7)

and 5c (Figure 8) were independently confirmed by X-ray crystal structure analysis. The

thioxanthone moiety is slightly twisted out of plane. The structures of all products were

confirmed by spectroscopic methods.

Figure 7: Molecular structure of compound 5b

5 6 Ar1 %(5)a Ar2 %(6)a

a 4-(MeO)C6H4 87

b a 4-EtC6H4 84 2-(MeO)C6H4 82

c b 4-tBuC6H4 75 4-(MeO)C6H4 79

d 3,5-Me2C6H3 82

e C6H5 71

f c 4-ClC6H4 78 3,4-(MeO)2C6H3 71

g 3-(CF3)C6H4 81

h 4-FC6H4 80

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Figure 8: Molecular structure of compound 5c

Compounds 6a-c were synthesized by two steps. After isolation of the products of the mono-

adducts 5b,c,f from the first step, the second arylboronic acids 3a,h,k were added for the second

cross-coupling reaction which afforded 1,3-diarylthioxanthones 6a-c in 71-82% yields (Scheme

3, Table 2). It is important to carry out the first coupling reaction at 60°C for 8 h using THF as a

suitable solvent for this step to improve the yield and site-selectivity. The second coupling cross-

coupling step was done at 90°C for 6 h using 1,4-dioxane as a solvent. Very good yields are

again obtained to prepare the unsymmetrical 1,3-diarylthioxanthones 6a-c with both electron-

donating and withdrawing groups.

The structure of compound 6b was independently confirmed by X-ray crystal structure

analysis (Figure 9). The structures of all products were confirmed by spectroscopic methods.


��

Products 5a, 5f were selected for optimization studies (Table 3). Thioxanthone 5a is derived

from an electron-rich arylboronic acid, while 5f is derived from an electron-poor arylboronic

acid. During the optimization we have found that the best yields were obtained when the

reactions were carried out at 60°C.

Table 3: Optimization table for synthesis of 5a, 5f at 60°C for 8 h

a (1.5equiv.) per (0.197 mmol) of 2. b (5ml) per (0.197 mmole) of 2. c (5mol%) per (0.197 mmole) of 2. (d ,e) Yield of isolated product.

Higher temperatures led to the formation of significant amounts of bis-arylated products. In

addition, it is important to use exactly 1.1 equiv. of the arylboronic acids per cross-coupling

reaction. The use of 1,4-dioxane as the solvent gave the best results in the case of the synthesis of

1,3-diarylthioxanthones 4. It was observed that employment of THF was advantageous in the

case of monoarylated products 5. The employment of potassium phosphate gave better yields

than the use of an aqueous solution of potassium carbonate, The use of Pd(PPh3)4 gave higher

yields than Pd(PPh3)2Cl2.

The sequential addition of two different arylboronic acids to 2 allowed for the direct synthesis

of 1,3-diarylthioxanthone 6d in only one step in 75% yield (Scheme 4, Table 4). Based on my

findings related to the synthesis of monoarylated products 5, the first step of the one-pot reaction

was carried out at 60°C while the second step was carried out at 90°C. One portion of the

catalyst (5 mol%) was added at the start of the reaction.

Entry Base(a) Solvent(b) Catalyst(c) % (5a)d % (5f)e

1 K2CO3 (1 mL, 2 M) dioxane [Pd(PPh)3Cl2] 35 24

2 K2CO3 (1 mL, 2 M) THF [Pd(PPh)3Cl2] 41 32

3 K2CO3 (1 mL, 2 M) dioxane [Pd(PPh3)4] 46 37

4 K2CO3 (1 mL, 2 M) THF [Pd(PPh3)4] 41 33

5 K3PO4 (1.5 equiv.) dioxane [Pd(PPh)3Cl2] 55 47

6 K3PO4 (1.5 equiv.) THF [Pd(PPh)3Cl2] 66 50

7 K3PO4 (1.5 equiv.) dioxane [Pd(PPh3)4] 63 57

8 K3PO4 (1.5 equiv.) THF [Pd(PPh3)4] 87 78

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Scheme 4: Synthesis of 6d. Reagents and conditions: i, 1) 2 (1.0 equiv.), 3l (1.1 equiv.),

Pd(PPh3)4 (5 mol%), K3PO4 (1.5 equiv.), 1,4-dioxane, 60"�� $%��3h (1.1 equiv.), 90°C, 6 h.

Table 4: Synthesis of 6d

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a Yields of isolated products

The Suzuki-Miyaura cross-coupling reactions of the bis(triflates) of 1,3-

dihydroxyanthraquinone proceeds by initial attack at position 1 (next to the carbonyl group)

which can be explained by the fact that position 1 is electronically more deficient than positions

2 and 3. In addition, a chelation of the catalyst by the carbonyl group might play a role. In

contrast, the Suzuki–Miyaura reactions of 2 proceed by initial attack at position 3. The different

site-selectivity is surprising. Obviously, the regiodirecting effect of the carbonyl group of this

compound seems to be less pronounced than in case of the bis(triflates) of 1,2- and 1,3-

dihydroxyanthraquinone. Therefore, the sterically less hindered position 3 was attacked first

(Figure 10).

3 6 Ar1 Ar2 %(6)a

l , h d 2-MeC6H4 4-(MeO)C6H4 75

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Figure 10: Possible explanation for the site-selectivity of the reactions of bis (triflate) 2

2.3 Conclusion

An efficient synthesis of different arylated thioxanthones by Suzuki-Miyaura cross-coupling

reactions of the bis(triflate) of 1,3-dihydroxythioxanthone was studied and reported. The

reactions were achieved with very good yields and excellent site-selectivity. The first attack

appeared at carbon atom C-3, while the second one was at C-1. The steric effect played an

important effect in this case and directed the selectivity in favour of carbon atom C-3.

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2.4 Site-Selective Suzuki–Miyaura Cross-Coupling Reactions of the

Bis(triflates) of 1,4-�Dihydroxy-9H-thioxanthen-9-one.

Results and discussion:

Palladium-catalyzed Suzuki cross-coupling reactions of the bis(triflate) of 1,4-dihydroxy-9H-

thioxanthen-9-one, which has been synthesized by a known procedure,47 was studied. 1,4-

Dihydroxy-9H-thioxanthen-9-one 7 was transformed into its bis(triflate) 8 in 87% yield (Scheme

5) by treatment with triflic anhydride in the presence of a mixture of Et3N and pyridine (1:2).

The triflic anhydride was added at -78oC under an argon atmosphere and the reaction mixture

was allowed to warm to room temperature and stirred for further 8 h. The best yields were

obtained when a mixture of base in this reaction was used.

Scheme 5: Synthesis of 8, Reagents and conditions: i, CH2Cl2, 7 (1.0 equiv.), Et3N/pyridine

(Mix.) 1:2(4.0 equiv.), Tf2O (2.4 equiv.), -78°C � 20°C, 8 h.

The Suzuki-Miyaura reaction of 8 with (2.4 equiv.) of arylboronic acids 3b,c,e,h,i,j resulted in

1,4-diarylthioxanthones 9a-f in (80-92%) yields (Scheme 6, Table 5). The reactions were carried

out nearly at the same conditions as reported for the synthesis of products 4.

Scheme 6:�Synthesis of 9a-f. Reagents and conditions: i, 8 (1.0 equiv.), 3b,c,e,h,i,j (2.4 equiv.),

Pd(PPh3)4 (10 mol%), K3PO4 (3.0 equiv.), THF, 90°C, 8 h.

��

Table 5: Synthesis of 9a-f


The best yields were obtained when the reactions were carried out using Pd(PPh3)4 (10 mol %)

as catalyst, K3PO4 (3.0 equiv.) as base and when the reaction was carried out using THF as a

solvent at 90°C for 8 h. The structures of all products were confirmed by spectroscopic methods.

Very good yields were obtained in both reactions for electron-rich and poor arylboronic acids.

1-Aryl-4-(trifluorosulfonyloxy)-thioxanthones 10a-i were synthesized by Suzuki cross-

coupling reaction of 8 with arylboronic acids 3b,c,e,f,h,i,j,l.m (1.1 equiv.). Different arylboronic

acids with both electron-donating and withdrawing group and sterically hindered arylboronic

acid (2-MeC6H4) were used for the synthesis. The reactions were achieved in high yields (76-

90%) and excellent site-selectivity (Scheme 7, Table 6). The best conditions for the synthesis of

mono-adducts were found when the reaction was carried out at 65°C for 8 h using Pd(PPh3)4 (5

mol% per cross-coupling reaction) as catalyst, K3PO4 (1.5 equiv.) as base and when the reaction

was carried out using THF as a solvent.

3 9 Ar 9 (%)a

b a 4-EtC6H4 80

c b tBuC6H4 83

e c 4-MeC6H4 84

h d 4-(MeO)C6H4 92

i e C6H5 91

j f 4-FC6H4 82

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Scheme 7:�Synthesis of 10a-i. Reagents and conditions: i, 8 (1.0 equiv.), 3b,c,e,f,h,i,j,l,m (1.1

equiv.), Pd(PPh3)4 (5 mol%), K3PO4 (1.5 equiv.), THF, 65°C, 8 h.

Table 6: Synthesis of 10a-i

3 10 Ar 10 (%)a

b a 4-EtC6H4 90

c b 4-tBuC6H4 76

e c 4-MeC6H4 87

f d 4-ClC6H4 84

h e 4-(MeO)C6H4 81

i f C6H5 88

j g 4-FC6H4 82

l h 2-MeC6H4 76

m i 3-MeC6H4 79


The structure of compound 10a (Figure 11) was independently confirmed by X-ray crystal

structure analysis. The aryl groups and the thioxanthone moiety are only slightly twisted out of

plane. The heterocyclic moiety is twisted out of plane. The structures of all products were

confirmed by spectroscopic methods.

��

Figure 11: Molecular structure of compound 10a

Products 10e, 10d were selected for optimization studies (Table 7). Thioxanthone 10e is

derived from an electron-rich arylboronic acid, while 10d is derived from an electron-poor

arylboronic acid.

Table 7: Optimization table for synthesis of 10e, 10d at 65Co for 8 h

Entry Base(a) Solvent(b) Catalyst(c) %(10e)d %(10d)e

1 K2CO3 Dioxane [Pd(PPh)3Cl2] 33 22

2 K2CO3 THF [Pd(PPh)3Cl2] 44 39

3 K2CO3 Dioxane [Pd(PPh3)4] 41 40

4 K2CO3 THF [Pd(PPh3)4] 42 33

5 K3PO4 Dioxane [Pd(PPh)3Cl2] 51 48

6 K3PO4 THF [Pd(PPh)3Cl2] 56 50

7 K3PO4 Dioxane [Pd(PPh3)4] 60 52

8 K3PO4 THF [Pd(PPh3)4] 81 84

a (1.5eq) per (0.197mmole) of 8. b (5ml) per (0.197mmol) of 8. c (5mol%) per (0.197 mmol) of 8. (d ,e) Yield of isolated product.

It was observed that the employment of THF as a solvent was advantageous in the case of the

synthesis of mono-adducts 10. Also, potassium phosphate gave better yields than the use of an

��

aqueous solution of potassium carbonate. The use of Pd(PPh3)4 (5 mol% per cross-coupling

reaction) gave higher yields than Pd(PPh3)2Cl2.

The structure of compound 10e was unambiguously confirmed by 2D-NMR techniques (Figure

12).

Figure 12: NOESY experiment of compound 10e

In the NOESY spectrum, an interaction was observed between the aromatic protons attached

to the carbon atom C-2 of thioxanthone ring to the aromatic protons of the attached boronic acid

ring attached to carbon atoms C-2' and C-6'. This confirmed that the first attack of boronic acid

takes place at carbon atom C-1 of the bis(triflate). These correlations are not observed, if the

boronic acid is attached to carbon atom C-4 of the bis(triflate).

The one-pot reaction of 8 with two different arylboronic acids allowed for the synthesis of 1,4-

diarylthioxanthones 11a-d in only one step and in very good yields (84-90%) (Scheme 8, Table

8).

Scheme 8:� Synthesis of 11a-d. Reagents and conditions: i, 1) 8 (1.0 equiv.), 3h,j,h,h (1.1

equiv.), Pd(PPh3)4 (5 mol%), K3PO4 (1.5 equiv.�� "��#�$%��3e,h,c,n (1.1 equiv.), 90°C,

6 h.

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Based on our findings related to the synthesis of mono-aryl products 5, the first step of the

one-pot reaction was carried out at 65°C and the second step was carried out at 90°C. One

portion of the catalyst (5 mol%) was added at the start of the reaction.

Table 8: Synthesis of 11a-d

a Yields of isolated products.��

The reaction of bis(triflate) 8 proceeds by initial attack at the sterically more hindered

position 1. This might be explained as follows: carbon atom C-1 is the most electron-deficient

position, but it is sterically more hindered than positions 4 and 3. In case of compound 2, the first

attack occurs at the sterically less hindered position 3. The attack to carbon atom C-4 of

thioxanthone 8 is hindered by the lone pairs of the sulfur atom. Therefore, the attack occurs at

position 1.

Figure 12: Possible explanation for the site-selectivity of the reactions of bis(triflates) 2 and 8

3 11 Ar1 Ar2 %(11)a

h , e a 4-(OMe)C6H4 4-MeC6H4 90

j , h b 4-FC6H4 4-(OMe)C6H4 88

h , c c 4-(OMe)C6H4 4-tBuC6H4 84

h , n d 4-(OMe)C6H4 3-ClC6H4 89

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2.5 Conclusion

The synthesis of various arylated thioxanthones by Pd(0)-catalyzed Suzuki cross-coupling

reactions of the bis(triflates) of 1,3- and 1,4-dihydroxy-9H-thioxanthen-9-one were studied and

reported. The first attack of the Suzuki reactions of 2 proceeded in favour of carbon atom C-3,

while for compound 8, the Suzuki reactions preceded in favour of carbon atom C-1. Electronic

and steric effects were the responsible reasons of the site-selective Suzuki reaction in 1,3- and

1,4-dihydroxy-9H-thioxanthen-9-one.

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3. Site-Selective Synthesis of Arylated-1H-inden-1-ones by Suzuki-Miyaura

Cross-Coupling Reactions of 2,3,5-Tribromo-1H-inden-1-one.

3.1 General Introduction

Arylated indenones represent a pharmacologically important molecular entity 48 For example,

2,3-diarylindenones have been studied as ligands for the estrogen receptor 48a. 3-Arylindenone-2-

carboxylic acid derivatives have been studied as selective inhibitors of fibroblast growth factor

receptor-1 tyrosine kinase48d. Indenones also occur in several biologically relevant natural

products, such as euplectin containing both a benzofuran and an inden-1-one substructure49.

Other examples include neo-lignans isolated from the fruits of Virola sebifera50. Pauciflorol F is

a 2,3-diarylindanone which has been prepared by palladium catalyzed Larock cyclization,

hydrogenation and subsequent epimerization51. 2,3-Diarylindenones are available by classic

methods which include, for example, intramolecular Friedel-Crafts acylations,52a reactions of

phthalides or 1H-indene-1,3(2H)-diones with Grignard reagents,52b,c and synthetic

transformations of dibenzoylmethane,52d benzophenone derivatives,52e or diphenyl acetylene52f.

Transition metal-catalyzed syntheses of 2,3-diarylinden-1-ones include the Larock cyclization51

and related processes53.

Reactions of functionalized indenones, such as hydrogenations, reactions of the carbonyl group

or conjugate additions, have been widely studied. We were interested in palladium-catalyzed

cross-coupling reactions of halogenated inden-1-ones. While reactions of 2,3-dibromo-1H-inden-

1-one with amines, Grignard reagents, and CH-acidic compounds were reported nearly a century

ago,54 transition metal-catalyzed reactions of this molecule were unknown until our recent

report55 in this field. Site-selective palladium catalyzed reactions of dibromofuranones, which are

closely related to 2,3-dibromoindenones, have been previously reported by Bellina and

coworkers56.

In general, site-selective palladium(0)-catalyzed cross-coupling reactions of polyhalogenated

heterocycles are of considerable current interest in organic chemistry because they allow a facile

assembly of complex heterocycles in only one step57,58.

I have studied what are, to the best of my knowledge, the first site-selective Suzuki-Miyaura

cross-coupling reactions of 2,3,5-tribromoinden-1-one. These reactions provide a convenient

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approach to various arylated inden-1-ones. Interestingly, my starting material, 2,3,5-tribromo-

1H-inden-1-one, represents a new compound which has, to the best of our knowledge, not been

synthesized or studied before.

Results and Discussion:

2,3,5-Tribromo-1H-inden-1-one 13 was prepared in 62% yield by reaction of commercially

available 5-bromoindan-1-one with NBS in the presence of AIBN (Scheme 9). While 2,3-

dibromoinden-1-one is known,59 the synthesis of 13 has, to the best of our knowledge, not been

previously reported.

Scheme 9: Synthesis of 13. Conditions: i, 12 (1.0 equiv.), NBS (3.5 equiv.), AIBN (10 mol %),

benzene, reflux, 7 h.

The Suzuki-Miyaura cross-coupling reaction of 13 with 3.3 equiv. of arylboronic acids

3i,b,c,o,n,j,g afforded the 2,3,5-triaryl-1H-inden-1-ones 14a-g in (76-88%) yields (Scheme 10,

Table 9). The best yields were obtained using 3.3 equiv. of the arylboronic acid, Pd(PPh3)4 (5

mol %) as catalyst, K2CO3 (2 M, 1 mL) as base and 1,4-dioxane as solvent at 70°C for 6 h.

Compounds 14 could be prepared in equally good yields using Pd(PPh3)2Cl2 as the catalyst.

Similar conditions were used for the Suzuki reaction of 2,3-dibromoinden-1-one55. Different

types of arylboronic acids were used in this reaction. The reactions were successful for both

electron-rich and electron-poor arylboronic acids. The highest yield was obtained using 3b as

electron-rich boronic acid (88%).

��

Scheme 10: Synthesis of 14a-g. Conditions: i, ArB(OH)2 3i,b,c,o,n,j,g (3.3 equiv.), Pd(PPh3)4 (5

mol%), K2CO3 (2 M, 1 mL), 1,4-dioxane, 70°C, 6 h.

Table 9: Synthesis of 2,3,5-triaryl-indenone 14a-g

3 14 Ar %(14) a

i a C6H5 83

b b 4-EtC6H4 88

c c 4-tBuC6H4 85

o d 3-(MeO)C6H4 76

n e 3-ClC6H4 79

j f 4-FC6H4 81

g g 3-(CF3)C6H4 78


Pd(0)-catalyzed Suzuki-Miyaura cross-coupling reactions of 13 with (1.0 equiv.) of

arylboronic acids 3i,c,n,g,p,e,h afforded the 3-aryl-2,5-dibromo-1H-inden-1-ones 15a-g in (78-

92%) yields and with excellent site-selectivity (Scheme 11, Table 10). The first attack occurred

at carbon atom C-3. The yields dropped when more than exactly (1.0 equiv.) of the boronic acids

were used. The reactions were carried out using Pd(PPh3)4 (3 mol % per cross-coupling reaction)

as the catalyst. In case of 15c, Pd(PPh3)2Cl2 (3 mol%) was employed as well. K3PO4 (1.5 equiv.)

was used instead of K2CO3 to achieve the best conditions for site-selectivity in the reaction.

��

Scheme 11: Synthesis of 15a-g. Conditions: i, ArB(OH)2 3i,c,n,g,p,e,h (1.0 equiv.), Pd(PPh3)4

OR Pd(PPh3)2Cl2 (3 mol %), K3PO4 (1.5 equiv.), 1,4-dioxane, 45°C, 9 h.

It is important to carry out the reactions at 45 instead of 70°C for this coupling. Significant

amounts of side-products, derived from multifold coupling, were formed when the temperature

was too high. The reactions could be successfully carried out with both electron-rich and poor

arylboronic acids. The highest yield was obtained using 3h as boronic acid among the other types

used for the reaction which afforded 15g in (92%) yield and excellent site-selectivity.

Table 10: Synthesis of 2,5-dibromo-3-aryl-indenone 15a-g

3 15 Ar % (15) a

i a C6H5 83

c b 4-tBuC6H4 86

n c 3-ClC6H4 82b

g d 3-(CF3)C6H4 80

p e 4-(OCF3)C6H4 78

e f 4-MeC6H4 86

h g 4-(MeO)C6H4 92

a Yields of isolated products,b Pd(PPh3)2Cl2 was used.

The structures of all products were confirmed by spectroscopic methods. The structure of 15d

was independently confirmed by X-ray crystal structure analysis 60 (Figure 13).The aryl group

and the indenone moiety is twisted out of plane.

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Figure 13: Molecular structure of compound 15d

2,3-Diaryl-5-bromo-1H-inden-1-one 16a-g was prepared by reaction of 13 with (2.0 equiv.)

of arylboronic acids 3b,c,o,j,g,h,f in (75-88%) yields (Scheme 12, Table 11). The best yields

were obtained using exactly (2.0 equiv.) of the arylboronic acids, Pd(PPh3)4 (5 mol %) as

catalyst, K3PO4 (3.0 equiv.) as base with 1,4-dioxane at 60°C for 6 h. The reactions were

successful for both electron-rich and poor arylboronic acids (Table 11) and the structures of all

products were confirmed by spectroscopic methods.

Scheme 12: Synthesis of 16a-g. Conditions: i, ArB(OH)2 3b,c,o,j,g,h,f (2.0 equiv.), Pd(PPh3)4 (5

mol %), K3PO4 (3.0 equiv.), 1,4-dioxane, 60°C, 6 h.

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Table 11: Synthesis of 5-bromo-2,3-diaryl-indenone 16a-g

3 16 Ar % (16) a

b a 4-EtC6H4 88

c b 4-tBuC6H4 83

o c 3-(MeO)C6H4 75

j d 4-FC6H4 78

g e 3-(CF3)C6H4 77

h f 4-(MeO)C6H4 85

f g 4-ClC6H4 87


The structure of 16g was independently confirmed by X-ray crystal structure analysis (Figure

14). The aryl groups and the indenone moiety are twisted out of plane.

Figure 14: Molecular structure of compound 16g

��

The one-pot synthesis reaction of 13 with two different arylboronic acids, which were

sequentially added, afforded the unsymmetrical 2,3-diaryl-5-bromo-1H-inden-1-ones 17a-c

containing two different aryl groups (Scheme 13, Table 12). To achieve a good site-selectivity in

favour of position 3 of the substrate, it was proved that the first coupling step should carried out

at 45°C for 9 h and the second step at 60°C for 6 h.

Scheme 13: Synthesis of 17a-c. Conditions:1) Ar1B(OH)2 3b,f,f (1.0 equiv.), Pd(PPh3)4 (5

mol%), K3PO4 (3.0 equiv.), 1,4-dioxane, 45°C��'�$% 2) Ar2B(OH)2 3h,b,h (1.0 equiv.), 60°C, 6 h.

Table 12: Synthesis of 17a-c


The one-pot reaction was carried out in one step without isolating the first cross-coupling

product. The second boronic acids 3h,b,h was added after a period of 9 h for the first coupling

reaction (which was done at 45°C) to ensure full conversion of the starting material of the first

coupling product. The reaction was carried out in very good yields (79-82%) and excellent site-

selectivity.

The synthesis of the 2,3,5 triaryl-1H-inden-1-ones containing two different arylboronic acids

were studied also and afforded 18a-c. The reaction of 15g with (2.2 equiv.) of 3c afforded 18a in

(78%) yield (Scheme 14, Table). The one-pot reaction of 13 with (1.0 equiv.) of 3f and with (2.2

3 17 Ar1 Ar2 % (17)a

b , h a 4-EtC6H4 4-(MeO)C6H4 80

f , b b 4-ClC6H4 4-EtC6H4 79

f , h c 4-ClC6H4 4-(MeO)C6H4 82

��

equiv.) of 3b afforded 18b in (81%) yield. Compound 18c was prepared in very good overall

yield (84%) (Scheme 14, Table 13).

During the synthesis of 18a-c as a one-pot reaction (sequential addition), the temperature and

the stoichiometry again played an important role.

Scheme 14: Synthesis of 18a-c. Conditions: i, Ar1B(OH)2 3f,f (1.0 equiv.), Pd(PPh3)4 (5 mol%),

K3PO4 (4.5 equiv.), 1,4-dioxane, 45°C, 9 h, : ii, Ar2B (OH)2 3b,h (2.2 equiv.), 60°C, 6 h, : iii,

Ar2B(OH)2 3c (2.2 equiv.), Pd(PPh3)4 (5 mol%), K2CO3 (2 M, 1 mL), 1,4-dioxane, 70°C, 6 h.

Table 13: Synthesis of 18a-c

3 18 Ar1 Ar2 % (18)a

h , c a 4-(MeO)C6H4 4-tBuC6H4 78b

f , b b 4-ClC6H4 4-EtC6H4 81c

f , h c 4-ClC6H4 4-(MeO)C6H4 84c

a Yields of isolated products, b Yields based on 15g, c Overall yield based on 13.

��

The reaction of 16d with (1.1 equiv.) of 3o afforded 19a in (88%) yield (Scheme 15, Table

14). The one-pot synthesis reaction (sequential addition) of 13 with (2.2 equiv.) of 3q and with

(1.1 equiv.) of 3h afforded 19b in (86 %) yield.

Scheme 15: Synthesis of 19a,b. Conditions: i, Ar1B(OH)2 3q (2.0 equiv.), Pd(PPh3)4 (5 mol%),

K3PO4 (4.5 equiv.), 1,4-dioxane, 60°C, 6 h: ii, Ar2B(OH)2 3h (1.1 equiv.), 70°C, 6 h: iii, 16d (1.0

equiv.), Ar2B(OH)2 3o (1.1 equiv.), Pd(PPh3)4 (3 mol%), K2CO3 (2 M, 1 mL), 1,4-dioxane, 70°C,

6 h.

Table 14: Synthesis of 19a, 19b

3 19 Ar1 Ar2 %(19)a

j , o a 4-FC6H4 3-(MeO)C6H4 88b

q , h b 4-(CF3)C6H4 4-(MeO)C6H4 86c

a Yields of isolated products, b Yield based on 16d,

c Overall yield for one-pot synthesis based on 13.

During the optimization of the one-pot synthesis of compounds 19a, 19b, the temperature was

60°C for the first cross-coupling step and was then increased to 70°C for the second step. The

stoichiometry (2.0 equiv. for the first step and 1.1 equiv. for the second step) proved to be

important. The structure of 19b was independently confirmed by X-ray crystal structure analysis 60 (Figure 15). Two of the three aryl groups of 19b are twisted out of plane.

��


The development of a site-selective one-pot process, which sequentially introduces three

different aryl groups in one step, failed. However, the synthesis of such molecules can be

realized by reaction of 2,3-diaryl-5-bromoinden-1-ones 17a-c with arylboronic acids.

The order of the reactivity of the three different positions of 2,3,5-tribromoinden-1-one is C-

3 > C-2 > C-5. The site-selectivity can be explained by the fact that carbon atom C-3 is

considerable more electron-deficient than positions 2 and 5. The second attack occurred at

carbon atom C-2 which is sterically more hindered than position 5 and electronically less

deficient.

This result was surprising because it does not follow the rule suggested by Handy and Zhang

for the prediction of the site-selectivity of palladium-catalyzed reactions of polyhalogenated

substrates. For the prediction of the selectivity, the 1H NMR spectrum of the non-halogenated

parent compounds is studied which reflects the electronic situation of the different positions.

According to the rule of the authors, the first attack should occur at that position which has the

higher chemical shift value of the respective proton. In case of the 1H NMR spectrum of inden-1-

one, which is the parent molecule of 2,3,5-tribromoinden-1-one 13, the chemical shift of proton

5-H is significantly shifted downfield with regard to proton 2-H which is the most up-field

resonating proton of the molecule. In contrast, proton 3-H resonates most downfield of all

protons of inden-1-one. Therefore, the rule of Handy and Zhang correctly predicts the selectivity

in favour of position 3, but not the selectivity in favour of position 2 (with respect to position 5).

The selectivity in favour of position 5 might be explained by chelation of the catalyst to the

carbonyl oxygen atom which may enhance the rate in favour of position 2 (Figure 16).

��

Figure 16: Possible explanation for the site-selectivity of the reactions of 13

��

3.2 Conclusion

I have studied the site-selective Suzuki-Miyaura cross-coupling reactions of 2,3,5-tribromo-

1H-inden-1-one, a novel brominated indenone derivative, which provide a convenient and site-

selective approach to various arylated inden-1-ones in good yields. The order of the selectivity is

C-3 > C-2 > C-5. Carbon atom C-3 is the most electron deficient position; thus, the first attack

takes place there. The selectivity in favor of position C-2 can be explained by chelation of the

catalyst to the neighboring carbonyl group.

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4. Synthesis of Arylated 1-Methyl-1H-indoles by Suzuki-Miyaura Cross-

Coupling Reactions of 2,3,6-Tribromo-1-methyl-1H-indole.

4.1 General Introduction Alkaloids are groups of natural products containing nitrogen in a cyclic system and occur

naturally in plants and other living organisms. These types of compounds nearly always contain

their nitrogen as part of a heterocyclic system with few exceptions and are often complex in

structure and usually show specific pharmacological activity. For example, some alkaloids show

antifungal activity such as the aporphine alkaloid liriodenine which displays a broad activity

spectrum against fungi, such as the yeast Candila albicans, Trichophyton mentagrophytes, and

has high activity against phytopathogenic fungi61.

Many reviews have been written on indole and its derivatives62,63. A wide variety of naturally

occurring, biologically active brominated indole alkaloids have been isolated from marine

invertebrates, including bryozoans, coelenterates, sponges and tunicates. 2,3,6-Tribromo-1-

methyl-1H-indole has been isolated from red alga Laurencia brongniartii which possess anti-

bacterial and anti-fungal properties. In addition, the central importance of the indole derivatives

in living organisms has inspired chemists to design and synthesize indole-containing

compounds64. Arylated indoles are of considerable pharmacological relevance, due to their anti-

inflammatory, anti-arthritic and anti-pyretic properties65. For example 2,3-bis(4-

methoxyphenyl)indole ((indoxole() has been shown to possess a stronger anti-inflammatory

activity than common drugs, such as aspirin and indomethacin66 . Based on these findings, novel

COX-2 inhibitors for the treatment of arthritic pain have recently been developed 67.

Many methods for the synthesis of N-methylarylindoles, for example the Fisher indole

synthesis, is the best known and most widely used method. The Ullman-type coupling

methodology, involving the combination of an indole with an aryl halide in the presence of base

and a copper catalyst at high temperatures, is an important alternative. Methods that operate

under milder conditions and utilize aryl bismuth and aryl lead reagents have been developed.

While all of these methods are useful in their own right, each of them suffers from one or more

limitations including a lack of generality, the use stoichiometric quantities of toxic reagents, or

the need to employ harsh reaction conditions68.�

In recent years, a number of site-selective palladium(0)-catalyzed cross-coupling reactions of

polyhalogenated heterocycles have been developed 69. The site-selectivity of these reactions is

��

generally influenced by electronic and steric parameters. Recently, Langer and coworkers

reported the synthesis of different aryl-substituted compounds using polyhalogenated substrates

and also reported the site-selective Suzuki-Miyaura cross-coupling reactions of 2,3-dibromo-1-

methyl-1H-indole19a-h.

A number of Suzuki-Miyaura reactions of mono-halogenated indoles have been reported70.

Ohta et al. studied the site-selective Suzuki-Miyaura reactions of N-TBDS-3,6-dibromoindole71.

The first attack occurred at carbon atom C-6. Gribble and Liu reported the synthesis of

symmetrical N-phenylsulfonyl-2,3-diarylindoles by twofold Suzuki-Miyaura reactions of 2,3-

dihalo-N-(phenylsulfonyl)indoles72. The reactions were carried out using Pd(OAc)2/P(o-Tol)3

and K2CO3 in acetone/H2O (2:1) or DMF (70°C).

The Suzuki-Miyaura reactions of N-sulfonyl- and N-acyl-2,3,4,5-tetrabromopyrrole and of

unprotected 2,3,4,5-tetrabromopyrrole gave unsatisfactory results (with regard to yield and site-

selectivity). In contrast, the reactions of N-methyl-2,3,4,5-tetrabromopyrrole proceeded in good

yields and with excellent site-selectivity. The synthesis of 2,3,6-triaryl-1-methyl-1H-indoles by

Suzuki-Miyaura cross-coupling reactions have, to the best of our knowledge, not been reported

before. The reactions indeed proceed in very good yields and excellent site-selectivity.


2,3,6-Tribromo-1-methyl-1H-indole 21 was prepared in (70%) yield using a known procedure, 27b from commercially available 1-methyl-1H-indole 20 with NBS (3.4 equiv.) (Scheme16).

Scheme 16:�Bromination of 1-methyl-1H-indole 20, Reagents and conditions: i, THF, NBS (3.4

equiv.), -78°C � 20°C, 14 h.�

The Pd(0)-catalyzed Suzuki-Miyaura cross-coupling reaction of 2,3,6-tribromo-1-methyl-1H-

indole� 21 with (3.4 equiv.) of arylboronic acids 3h,c,b,e,f,n,j,q,g afforded the 2,3,6-triaryl-1-

methyl-1H-indole 22a-i in (78-87%) yields (Scheme 17, Table 15). The best yields were

��

obtained using Pd(PPh3)4 (5 mol%) as a catalyst, K2CO3 (2 M, 1 mL) as base and 1,4-dioxane at

110°C for 8 h.

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Scheme 17:�Synthesis of 22a-i. Reagents and conditions: i, 21 (1.0 equiv.), 3h,c,b,e,f,n,j,q,g

(3.4 equiv.), Pd(PPh3)4 (5 mol%), K2CO3 (2 M, 1 mL), 1,4-dioxane, 110°C, 8 h.

Table 15: Synthesis of 2,3,6-triaryl-1-methyl-1H-indole 22a-i


Different types of arylboronic acid having both electron-donating and withdrawing groups

were used in the reaction (Table 15). The structures of all products were confirmed by

spectroscopic methods.

Products 22c, 22g were selected for optimization studies (Table 16). Compound 22c is

derived from an electron-rich arylboronic acid, while 22g is derived from an electron-poor

arylboronic acid. The best yields were obtained when the reactions were carried out at 110°C for

8 h. the use of 1,4-dioxane as solvent gave the best results; the employment of an aqueous

3 22 Ar % (22) a

h a 4-(MeO)C6H4 87

c b 4-tBuC6H4 85

b c 4-EtC6H4 82

e d 4-MeC6H4 87

f e 4-ClC6H4 85

n f 3-ClC6H4 80

j g 4-FC6H4 84

q h 4-(CF3)C6H4 82

g i 3-(CF3)C6H4 78

��

solution of potassium carbonate gave better yields than the use of potassium phosphate as base.

The use of Pd(PPh3)4 (5 mol%) gave higher yields than Pd(PPh)3Cl2 or Pd(OAc)2 (3 mol%),

(Cy)3P or SPhos (6 mol%) as a catalyst.

Table 16: Optimization table for synthesis of 22c, 22g

a Yields of isolated products.,all reactions were carried out in dioxane(110°C, 8h).

2,6-Diaryl-3-bromo-1-methyl-1H-indoles 23a-e was prepared by reaction of 21 with

arylboronic acids 3h,b,e,f,j (2.1 equiv.) The reaction was carried out in good yields (73-83%)

and excellent site-selectivity (Scheme 18, Table 17). The first attack occurred at carbon atom C-2

and C-6, while position 3 remained free. The reactions were best carried out at 90°C using

exactly (2.1 equiv.) of the boronic acid and (5 mol%) of Pd(PPh3)4 as a catalyst. Both electron

donating and withdrawing groups were examined in this reaction. K3PO4 (3.0 equiv.) was used

as a suitable base in this case instead of K2CO3.

Scheme 18:� Synthesis of 23a-e. Reagents and conditions: i, 21(1.0 equiv.), 3h,b,e,f,j (2.1

equiv.), Pd(PPh3)4 (5 mol%), K3PO4 (3.0 equiv.), 1,4-dioxane, 90°C, 8 h.

Entry Conditions %(22c)a %(22g)a

1 Pd(PPh)3Cl2 (5mol%),aq. K2CO3 (2 M) 55 48

2 Pd(PPh)3Cl2 (5mol%), K3PO4 (4.5 equiv.) 52 40

3 Pd(PPh3)4 (5mol%),aq. K2CO3 (2 M) 82 84

4 Pd(PPh3)4 (5mol%), K3PO4 (4.5 equiv.) 65 53

5 Pd(OAc)2(3mol%), SPhos (6mol%),aq.K2CO3 (2 M) 75 71

6 Pd(OAc)2(3mol%), (Cy)3P (6mol%),aq.K2CO3 (2 M) 63 52

7 Pd(OAc)2 (3mol%), (Cy)3P (6mol%), K3PO4 (4.5 equiv.)

53 48

� ��

Table 17: Synthesis of 23a-e


The structures of compound 23a (Figure 17) and compound 23b (Figure 18) were

independently confirmed by X-ray crystal structure analysis. Both aryl groups and the indole

moiety are twisted out of plane.

Figure 17: Molecular structure of compound 23a


3 23 Ar %(23)a

h a 4-(MeO)C6H4 83

b b 4-EtC6H4 79

e c 4-MeC6H4 73

f d 4-ClC6H4 80

j e 4-FC6H4 83

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The Suzuki-Miyaura cross-coupling reaction of 21 with arylboronic acids 3c,b,e,f (1.1 equiv.)

afforded the 2-aryl-3,6-dibromo-1-methyl-1H-indole 24a-d in (77-84%) yields and with a very

good site-selectivity (Scheme 19, Table 18).

Scheme 19:�Synthesis of 24a-d. Reagents and conditions: i, 21(1.0 equiv.), 3c,b,e,f (1.1 equiv.),

Pd(PPh3)4 (3 mol%), K3PO4 (1.5 equiv.), toluene/1,4-dioxane (4:1), 65°C, 8h.

The reactions were carried out using Pd(PPh3)4 (3 mol%) as the suitable catalyst. It is

important to carry out the reactions at 65°C instead of 90°C.



Compounds 24a, 24d were selected for optimization studies (Table 19). 24a is derived from

an electron-rich arylboronic acid, while 24d is derived from an electron-poor arylboronic acid.

During the optimization, we have found that the best yields were obtained when the reactions

were carried out at 65°C. Significant amounts of side-products, derived from multi-fold

coupling, were formed when the temperature was higher than 65°C. A solvent mixture of

toluene/1,4-dioxane (4:1), K3PO4 (1.5 equiv.) as base, and Pd(PPh3)4 (3 mol%) as a catalyst were

used. The structures of all products were confirmed by spectroscopic methods.

3 24 Ar % (24)a

c a 4-tBuC6H4 84

b b 4-EtC6H4 83

e c 4- MeC6H4 77

f d 4-ClC6H4 79

��

Table 19: Optimization table for the synthesis of 24a, 24d

Entry solvent base ligand Temp.°C % (24a)a % (24d)a

1 dioxane 2 M K2CO3 (PPh3)4Pd 70 °C mixture mixture

2 dioxane 2 M K2CO3 Cy3P, Pd(OAc)2 70 °C mixture mixture

3 dioxane 2 M K2CO3 SPhos, Pd(OAc)2 70 °C mixture mixture

4 dioxane 2 M K2CO3 (PPh3)2PdCl2 70 °C mixture mixture

5 dioxane 1.5eq. K3PO4 (PPh3)4Pd 65 °C mixture mixture

6 dioxane 1.5eq. K3PO4 Cy3P, Pd(OAc)2 65 °C mixture mixture

7 toluene 2 M K2CO3 (PPh3)4Pd 65°C No reaction

No reaction

8 toluene 2 M K2CO3 (PPh3)4Pd 70 °C No reaction

No reaction

9 dioxane/ toluene (1:1)

2 M K2CO3 (PPh3)4Pd 65 °C mixture mixture


1.5eq. K3PO4 (PPh3)4Pd 65 °C 30% 25%


1.5eq. K3PO4 (PPh3)4Pd 65 °C 84a% 79a%


The structure of compound 24b was independently confirmed by 2D-NMR experiments. In

the HMBC spectrum, the aromatic proton of the attached boronic acid at C-2' showed a strong

coupling with C-2 of the indole ring. The same is true also with the proton at C-6'.This

confirmed that the first attack of boronic acid 3b occurred at carbon atom C-2 of the

tribromoindole.

��

Figure 19: 2D-NMR correlations of the compound 24b

Unsymmetrical 2,3,6-triaryl-1-methyl-1H-indoles 25a-d were prepared by site-selective

Suzuki cross-coupling reactions. A one-pot synthesis was carried out for product 25a. The first

cross-coupling reaction happened by reaction of 21 with (1.1 equiv.) of 3j at 65°C �)��#�$%�K3PO4

(1.5 equiv.) as a base, a mixture of solvents toluene/ 1,4-dioxane (4:1), and Pd(PPh3)4 (5 mol%)

as catalyst were used. Then, 3c was added (2.1 equiv.) for the second cross-coupling reaction

which afforded product 25a in good yield (74%) containing two different aryl groups. Based on

our finding for the synthesis of 24a-d, compounds 25b-d was synthesized in two steps. After

isolating the first product of the first cross-coupling step, the second boronic acid was added for

the second catalysed cross-coupling reaction.

Products 25b-d were isolated in good yields (72-82%) (Scheme 20, Table 20). To achieve a

good site-selectivity in favour of position 2 of the substrate, it is important that the first step is

carried out at 65°C for 8 h and the second step at 90°C for the period of 8 h. In both steps

Pd(PPh3)4 was used as a catalyst. Both electron-donating and withdrawing groups were examined

for the synthesis of compounds 25a-d.

Scheme 20:�Synthesis of 25a-d. Reagents and conditions: i, 1) Ar1B(OH)2 3j,c,f,c (1.1 equiv.) ,

Pd(PPh3)4 (5 mol%), K3PO4 (1.5 equiv.), toluene/1,4-dioxane (4:1), 65°C, 8 h, 2) Ar2B(OH)2

3c,h,h,a (2.1 equiv.), K2CO3 (2 M, 1 mL), 1,4-dioxane, 90°C, 8h.

��


a Yields of isolated products, b,d Yields based on 24a,24d

c Yields based on 21 as one-pot reaction.

The order of reactivity of the three different positions of 2,3,6-tribromo-1-methyl-1H-indole is

C-2 > C-6 > C3. The first attack was happened at carbon atom C-2. The site-selectivity can be

explained by the fact that carbon atom C-2 is considerable more electron-deficient than positions

3 and 6. The second attack occurred at position 6 which is sterically less hindered than position 3

and electronically less deficient than position 2. Carbon atom C-3 is more hindered and more

electron-deficient than C-6.

Figure 20: Possible explanation for the site-selectivity of the reactions of 21

3 25 Ar1 Ar1 %(25)a

j , c a 4-FC6H4 4-tBuC6H4 74c

c , h b 4-tBuC6H4 4-(OMe)C6H4 81b

f , h c 4-ClC6H4 4-(OMe)C6H4 82d

c , a d 4-tBuC6H4 2-(OMe)C6H4 72b

��

4.2 Conclusion

Pd(0)-catalyzed site-selective Suzuki-Miyaura cross-coupling reactions of 2,3,6-tribromo-1-

methyl-1H-indole afforded various arylated indoles in high yield and excellent site-selectivity.

The site-selectivity can be explained according to electronic and steric reasons. The order of the

selectivity is C-2 > C-6 > C-3. Carbon atom C-2 is the most electron-deficient and it was the first

position attacked.

.

��

5. Synthesis of Functionalized Anthraquinones by Domino Twofold Heck-6π-

Electrocyclization Reactions of 2,3-Dibromonaphthaquinone.

5.1 General Introduction

Anthraquinones or anthracene-9,10-diones are essential chemical constituents of fungi,

lichens and higher plants which possess a broad spectrum of biological activities including

antibacterial, anti-inflammatory, and antiviral properties73a,b. For example, the anthracyclines

constitute an important class of antitumor agents and antibiotics, which include several

prominent compounds such as daunorubicin, adriamycin and aclarubicin74.

Most naturally occurring anthracyclines are isolated in O-glycosylated form, but some of

them, such as saintopin, are found as aglycons70. Simple hydroxylated anthraquinones (such as

chrysophanic acid, vismiaquinone, anthragallol, questin, and several others) are also widely

distributed in nature76a,b. While most of them are found as aglycons, some derivatives, such as

pulmatin, occur in O-glycosylated form77.

Anthraquinone derivatives show a very good antitumor activity against cancer cells78. On the

other hand, anthraquinones are widely used as antihelminthic as well as inhibitor agents79. Many

applications of aryl-substituted anthraquinones exist in material sciences, due to their redox, UV

and luminescence properties80a-d. They have been also used as stabilizers of light-modulating

fluids. Anthraquinones provide the basis of several natural dyes as well81.

Current methods for the synthesis of anthraquinones are based on regioselective annulation

reactions, such as Diels-Alder cycloadditions of naphthaquinones, reactions of lithiated species

with suitable electrophiles, and Friedel-Craft condensations82.

Palladium-catalyzed coupling reactions of Heck type is the most versatile method for C-C

bond formation83. Application of the Heck reaction in the synthesis of natural and non-natural

products is well reviewed by de Meijere and Meyer84. Extensive methodological refinements

over the last decade, particularly with regard to solvents, catalysts and additives, have greatly

improved the synthetic efficiacy of these reactions, as a result of which they are now finding

almost routine use in complex organic synthesis. Polyhalogenated molecules represent

interesting substrates in Pd(0)-catalyzed cross-coupling reactions69. In this chapter, I show my

results related to the synthesis of functionalized anthraquinones by domino85 twofold Heck-6π-

electrocyclization reactions of 2,3-dibromonaphthoquinone.

��


Different types of acrylates and styrenes 27a-j with both electron-donating and withdrawing

groups were used in this study. The Heck reaction of 2,3-dibromonaphthoquinone 26 with 27a

(2.5 equiv.) afforded 28a in 76% yield (Scheme 21, Table 21). The formation of 28a can be

explained by twofold Heck reaction (intermediate A) and subsequent 6π-electrocyclization to

give intermediate B. Dehydrogenation of the latter afforded 28a. The best yields were obtained

when the reactions were carried out using Pd(OAc)2 (5 mol%) and the biaryl mono-phosphine

ligand XPhos (10 mol%), which was recently developed by Buchwald and co-workers 18 (Figure

21).

Scheme 21: Synthesis of 28a-j and 29a-j. Conditions: i, method 1) Pd(OAc)2 (5 mol%), XPhos

(10 mol%), NEt3 (8.0 equiv.), DMF, 90°��#�$% method 2) ii, Pd(OAc)2 (5 mol%), XPhos (10

mol%), NEt3 (8.0 equiv.), DMF, 110°C, 8 h.

The reaction was carried out in DMF at 90°C for 8 hours (method 1). The temperature played

an important role in these reactions. The yields significantly decreased when the temperature was

increased. A clean reaction was observed when it was carried out at 90°C.

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Compound 29a was isolated as a separable mixture in 44% yield following method 2 (110°C).

Decomposition was observed when the reaction was carried out at temperatures higher than

120°C. The formation of 29a, which contains only one alkyl group, can be explained by the fact

that thermal conditions have an effect on the electrocyclization providing intermediate B.

Figure 21: Biaryl mono-phosphine ligands developed by Buchwald and co-workers

Table 21: Synthesis of 28a-j and 29a-j

28,29 27 Method 1,

Yield of 28(%)a

Method 2,

Yields of 28and 29(%)a

a 4-ClC6H4 76 Traces+44 b 3-ClC6H4 71 _b

c 4-tBuC6H4 80 _b

d 4-MeC6H4 78 _b

e 4-FC6H4 72 _b

f 4-tBuOC6H4 _b Traces+59 g CO2Et 79 25+37 h CO2tBu 82 30+60 i CO2iOctadecyl _b Traces+46 j CO2EtMeO _b Traces+71

a Yields of isolated products. b Experiment was not carried out.

The Heck reaction of 2,3-dibromonaphthoquinone 26 with styrenes 27b-e afforded 28b-e in

(71-80%) yields (method 1). When we have applied the reactions using method 2, compound 29f

was isolated in (59%) yield as a separable mixture; 27f was used as alkene for this reaction

��

(Scheme 1, Table 1). All products were confirmed by spectroscopic methods. The structure of

compound 28c was confirmed independently by X-ray crystallography (Figure 22).

Figure 22: Molecular structure of compound 28c

��

The Pd(OAc)2 catalyzed reaction of 26 with acrylates 27g, 27h afforded anthraquinones 28g

(79%), 28h (82%) following method 1. At higher temperature (110°C) and using method 2, a

separable mixture of 28g,h and 29g,h was obtained, respectively (Scheme 21, Table 21). Educt

27j afforded 29j in 71% yield. The product distribution was again dependent on the reaction

temperature. All products have been confirmed by spectroscopic methods.

Compound 28g was used for the optimization of the conditions for this project (Table 22). We

have found that di-substituted anthraquinones 28 were generally formed in good yields when the

reaction was carried out at 90°C, while mono-substituted anthraquinones 29 were predominantly

formed at 110°C as a separable mixture with 28. Pd(OAc)2 (5mol%) and XPhos (10 mol%) was

used as an efficient catalyst for such type of reactions. The choice of the solvent also played an

important role. No conversion was observed for non-polar solvents such as toluene. The

successful employment of DMF can be explained by its polarity and high boiling point.

��

Table 22: Optimization table for synthesis of 28g

a Yields of isolated products,all reactions were carried out in DMF and NEt3 as a base,

b Yield of isolated by-product 29g

5.2 Conclusion

An efficient synthesis of functionalized anthraquinones by domino ‘twofold Heck-6π-

electrocyclization’ reactions of 2,3-dibromonaphthoquinone was studied. The products, which

are not readily available by other methods, were formed in only one step under relatively mild

conditions. The temperature played an important role during the optimization of the reaction

conditions.

Entry Catalyst Temp.°C (28g)a %

1 Pd(OAc)2 (5 mol%), P(Cy)3 (10 mol%) 90 40

2 Pd(PPh3)2Cl2 (5 mol%) 90 25

3 Pd(PPh3)4 (5 mol%) 90 30

4 Pd(OAc)2 (5 mol%), XPhos (10 mol%) 120 25+37b

5 Pd(OAc)2 (5 mol%), XPhos (10 mol%) 90 79

��

6. Abstract

Due to the importance and wide-range applications of carbon-carbon bond forming reactions

in organic synthesis, palladium(0)-catalyzed Suzuki cross-coupling reactions of 1,3- and 1,4-

dihydroxy-9H-thioxanthen-9-one, 2,3,5-tribromoinden-1-one, 2,3,6-tribromo-1-methyl-1H-

indole and Heck reactions of 2,3-dibromonaphthaquinone were studied in my thesis. The Pd(0)-

catalyzed Suzuki cross-coupling reaction of the bis(triflates) of 1,3-dihydroxythioxanthones

afforded 1,3-diarylthioxanthones in high yields and excellent site-selectivity. The site-selectivity

was explained by steric-hindered effect, while electronic effect was responsible for the site-

selective Suzuki cross-coupling reaction of the bis(triflates) of 1,4-dihydroxythioxanthones. A

wide scope of symmetrical and unsymmetrical aryl indenones and indoles from brominated

substrates were synthesized using Pd(0)-catalyzed Suzuki cross-coupling reactions. Electronic

and steric parameters again played an important role for the site-selectivity. An efficient

synthesis of substituted anthraquinones by domino twofold Heck-6�-electrocyclization reactions

of 2,3-dibromonaphthaquinone was studied. The products were formed in only one step under

relatively mild conditions. The temperature played an important effect during the optimization.

In German��

Aufgrund der großen Bedeutung und breiten Anwendbarkeit von C-C-Knüpfungsreaktionen

in der organischen Synthese wurden in meiner Dissertation Palladium(0)-katalysierte Suzuki-

Kreuzkupplungsreaktionen an 1,3- und 1,4-Dihydroxy-9H-thioxanthen-9-on, 2,3,5-

Tribrominden-1-on, 2,3,6-Tribrom-1-methyl-1H-indol sowie Heck-Reaktionen an 2,3-

Dibromnaphthochinon in großem Umfang untersucht. Die Palladium(0)-katalysierte Suzuki-

Kreuzkupplung an Bis(triflaten) von 1,3-Dihydroxythioxanthonen ergab 1,3-Diarylthioxanthone

in hohen Ausbeuten und mit hoher Regioselektivität. Die Regioselektivität lässt sich in diesem

Fall durch sterische Hinderung erklären, während sie bei Bis(triflaten) von 1,4-

Dihydroxythioxanthonen von elektronischen Effekten gesteuert wird.

Darüber hinaus wurden mittels Palladium(0)-katalysierter Suzuki-Kreuzkupplungsreaktionen in

großem Umfang symmetrisch und unsymmetrisch substituierte Arylindenone und -indole

ausgehend von bromierten Ausgangsstoffen dargestellt. Auch hier spielten sterische und

elektronische Einflüsse eine große Rolle hinsichtlich der Regioselektivität.

��

Außerdem wurde eine effiziente Synthese von substituierten Anthrachinonen durch eine

zweifache Heck-6� / Electrocyclisierungsreaktion ausgehend von 2,3-Dibromnaphthochinon

erschlossen. Die Produkte wurden in nur einem Schritt unter relativ milden Bedingungen

gebildet. Dabei spielte die Temperatur eine entscheidende Rolle.

��

7. Experimental Section 7.1 General: Equipment, Chemicals and Work Technique

Reactions were carried out under inert atmosphere (Argon 4.6) in order to simultaneously

exclude oxygen and water when appropriate. Pressure tubes were used to avoid condenser.

Solvents for reactions were dried and distilled by standard methods or purchased from Merck,

Aldrich, Acros Organics, and others whenever exclusion of water was desired. Solvents for

liquid chromatography and extraction were always distilled prior to use and partly reused after

fractional distillation (n-heptane, ethyl acetate).

1H NMR Spectroscopy: ��+��,��!��+��*-��!!��+��*-��!!%�� = 0.00 ppm for

��.�/0�.$1�2��/3�%� 4� 5� � !�� 660� �)�� 7�.)3�-d6; � = 7.26 ppm for (CDCl3�%� � �!� 660� �)��

DMSO-d; Characterization of the signal fragmentations: s = singlet, d = doublet, dd = double of

doublet, t = triplet, q = quartet, m = multiplet, br = broadly. Spectra were evaluated according to

first order rule. All coupling constants are indicated as (J).

13C NMR Spectroscopy: ��+��,��!�� '��8�%��+��,��*-��!!��9��8��+��,�

ARX 500, (125 MHz) Ref: 29.84 ± 0.01 ppm and 206.26 ± 0.13 ppm for (CD3)2CO. d = 128.00

ppm for benzene-d6; � = 77.00 ppm for CDCl3. The multiplicity of the carbon atoms was

determined by the DEPT 135 and APT technique (APT = Attached Proton Test) and quoted as

CH3, CH2, CH and C for primary, secondary, tertiary and quaternary carbon atoms.

Characterization of the signal fragmentations: quart = quartet the multiplicity of the signals was

determined by the DEPT recording technology and/or the APT recording technology.

Mass Spectroscopy: AMD MS40, AMD 402 (AMD Intectra), Varian MAT CH 7, MAT 731.

High Resolution mass spectroscopy: ��33�:/3��'��)��;/��/3��%��+��<*��

AMD 402 (AMD Intectra).

��

Infrared Spectroscopy (IR)

Nicolet 205 FT-IR, Nicolet Protége 460 FT-IR. Peaks are given the following assignments: w =

weak, m = medium, s = strong.

Elemental Analysis

LECO CHNS-932, Thermoquest Flash EA 1112.

Melting Points

Micro heating table HMK 67/1825 Kuestner (Büchi Apparatus), Leitz Labolux 12 Pol with

heating table Mettler FP 90. Melting points are uncorrected.

X-ray Structures

Bruker X8Apex diffractometer with CCD camera (Mo K= radiation and graphite

monochromator, > = 0.71073 Å).

Column Chromatography: Chromatography was performed over Merck silica gel 60 (0,063 -

0,200 mm, 70 - 230 mesh) as normal and/or over mesh silica gel 60 (0,040 - 0,063 mm, 200 -400

mesh) as Flash Chromatography. All solvent were distilled before use.

Thin Layer Chromatography (TLC): Merck DC finished foils silica gel 60 F 254 on

aluminum foil and Macherey finished foils Alugram ® Sil G/UV254. Detection under UV light

with 254 nm and/or 366 nm without dipping reagent, as well as with anisaldehyde sulfuric acid

reagent (1 mL anisaldehyde consisting in 100 mL stock solution of 85% methanol, 14% acetic

acid and 1% sulfuric acid).

��

7.2 General Procedures

Site-Selective Suzuki–Miyaura Reactions of the Bis(triflate) of 1,3-Dihydroxythioxanthone

Synthesis of 9-oxo-9H-thioxanthene-1,3-diyl bis(trifluoro-methanesulfonate) (2): To a

solution of 1 (0.34g, 1.39 mmol) in CH2Cl2(20 mL) was added

Et3N (0.77 mL, 5.56 mmol), at 20°C under an argon atmosphere.

After stirring for 10 min at -78°C, Tf2O (0.56 mL, 3.34 mmol) was

added. The mixture was allowed to warm to 20°C and stirred for further 8 h. The reaction

mixture was filtered and the filtrate was concentrated in vacuo. The residue was

chromatographed without work up (flash silica gel, heptanes-EtOAc) and 2 was isolated as a

yellow solid (0.57 g, 80%), Mp.149-150°C. 1H NMR (300 MHz, CDCl3): � = 7.11(d, 1H,

J = 2.37 Hz, ArH), 7.45-7.51(m, 3H, ArH), 7.58-7.65 (m, 1H, ArH), 8.50 (dd, 1H, J = 1.02,

8.50 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -72.3, -73.2. 13C NMR (62.9 MHz, CDCl3):

� = 114.7 (CH), 118.6 (q, JF,C = 321.3 Hz, CF3), 118.7 (q, JF,C = 320.9 Hz, CF3), 118.9, 125.4,

127.7 (CH), 129.9 (C), 130.3, 133.3 (CH), 134.3, 142.7, 149.9, 150.8 (C), 177.8 (CO). IR (KBr):

v = 3081, 3030, 2958, 2923, 2851, 1728 (w), 1602, 1599, 1590 (m), 1554, 1465 (w), 1426 (s),

1399 (m), 1317, 1295 (w), 1246 (m), 1198 (s), 1150 (m), 1133, 1099 (s), 1080 (m), 1033 (w),

989, 929, 904, 884, 819, 807, 798 (m), 768 (w), 751, 714 (m), 684, 666, 655, 635 (w), 590, 569,

542, 530 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 508 ([M+H]+, 100), 347 (28), 283 (62), 255

(19). HRMS (EI, 70 eV): calcd for C15H6F6O7S3 [M]+,��!9 '�9��%��)�34,��!9 '� #'! ��

General Procedure for Suzuki–Miyaura cross-coupling Reactions: A THF solution (4-5 mL),

K3PO4 (1.5 equiv. per cross-coupling), Pd(PPh3)4 (5 mol% per cross-coupling) and arylboronic

acid 3 (1.1 equiv. per cross-coupling) was stirred at 60-90°C for 8 h. After cooling to 20°C,

distilled H2O was added. The organic and the aqueous layers were separated and the latter was

extracted with CH2Cl2. The combined organic layers were dried (Na2SO4), filtered and the

filtrate was concentrated in vacuo. The residue was purified by column chromatography (flash

silica gel, heptanes-EtOAc).

��

Synthesis of 1,3-diarylthioxanthones 4a-g:

1,3-Bis(2-methoxyphenyl)-9H-thioxanthen-9-one (4a): Starting with 2 (100 mg, 0.197 mmol),

2-methoxyphenylboronic acid 3a (72 mg, 0.47 mmol), Pd (PPh3)4

(23 mg, 10 mol %), K3PO4 (125 mg, 0.59 mmol) and 1,4-dioxane (5

mL), 4a was isolated as a light 1��)?�2)��4�9��0:��'!@�%�reaction

temperature: 90°C for 8 h. Mp.163-165°C. 1H NMR (300 MHz,

CDCl3): � = 3.72 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 6.87 (dd, 1H,

J = 0.71, 8.19 Hz, ArH), 6.93 (d, 1H, J = 8.04 Hz, ArH), 6.97-7.02 (m, 2H, ArH), 7.19-7.36 (m,

6H, ArH), 7.46 (d, 2H, J = 1.79 Hz, ArH), 7.68 (d, 1H, J = 1.77 Hz, ArH), 8.23 (dt, 1H, J = 0.96,

8.01 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 55.5 (OCH3), 55.7 (OCH3), 110.3, 111.4,

120.7, 121.0, 125.3, 125.9, 126.1 (CH), 127.0 (C), 128.4, 129.1, 129.4, 129.8, 130.9, 131.5 (CH),

131.6 (C), 131.8 (CH), 132.7, 136.2, 137.1, 141.2, 141.5, 156.1, 156.3 (C), 181.0 (CO). IR

(KBr): v = 3377, 3056, 2997, 2930, 2833, 2247 (w), 1640, 1587 (s), 1536 (w), 1492, 1460, 1434

(s), 1485 (m), 1299, 1270 (m), 1238 (s), 1178, 1157, 1117 (m), 1074, 1057, 1047 (w), 1022 (s),

963 (w), 924 (m), 906, 877, 851(w), 834 (m), 807, 785, 771 (w), 746, 736, 722 (s), 678, 666 (m),

645, 615, 574, 552 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 423 ([M-H]+, 100), 394 (29), 377

(39). HRMS (EI, 70 eV): calcd for C27H20O3S [M]+: �� 99%��)�34,�� 9 ��

1,3-Bis(4-ethylphenyl)-9H-thioxanthen-9-one (4b): Starting with 2 (100 mg, 0.197 mmol),

4-ethylphenylboronic acid 3b (70 mg, 0.47 mmol), Pd(PPh3)4

(23 mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and 1,4-dioxane

(5 mL), 4b was isolated as a light 1��)?� 2)��4� 9�0:��#�@�%�

reaction temperature: 90°C for 8 h. Mp.179-181°C. 1H NMR

(300 MHz, CDCl3): � =1.18 (t, 3H, J = 7.59 Hz, CH3), 1.21 (t,

3H, J = 7.59 Hz, CH3), 2.60 (q, 2H, J = 7.59 Hz, CH2), 2.67 (q,

2H, J = 7.59 Hz, CH2), 7.17-7.22 (m, 6H, ArH), 7.26-7.32 (m, 1H, ArH), 7.40 (d, 1H, J = 1.86

Hz, ArH), 7.40-7.46 (m, 2H, ArH), 7.50 (d, 2H, J = 8.25 Hz, ArH), 7.64 (d, 1H, J = 1.86 Hz,

ArH), 8.26 (dd, 1H, J = 0.75, 8.49 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 15.3 (CH3), 15.5

(CH3), 28.6 (CH2), 28.7 (CH2), 122.9, 125.2 (CH), 125.9 (C), 126.1, 127.3, 127.4, 127.9, 128.6,

129.4, 129.8 (CH), 131.6 (C), 131.8 (CH), 135.9, 136.0, 138.9, 140.9, 142.6, 143.4, 145.1, 140.8

(C), 180.7 (CO). IR (KBr): v = 3050, 3022, 2961, 2927, 2891, 2871, 2853 (w), 1644 (s), 1612

(w), 1588 (s), 1556, 1537 (w), 1510 (m), 1469, 1455 (w), 1432 (m), 1380, 1316 (w), 1298 (s),

1286 (m), 1231, 1184, 1162 (w), 1152, 1115, 1074 (m), 1051 (w), 1031 (m), 1017, 966 (w), 924

��

(m), 892, 875(w), 833 (m), 821 (s), 770 (w), 749, 720 (s), 672 (m), 659, 651, 640, 615, 591, 574,

566 (w), 553 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 420 ([M]+, 53), 419 ([M-H]+, 100), 404

(11). HRMS (EI, 70 eV): calcd for C29H23OS [M-H]+: ��' �� %��)�34,��' ��9'

1,3-Bis(4-(tert-butyl)phenyl)-9H-thioxanthen-9-one (4c): Starting with 2 (100 mg, 0.197

mmol), 4-tert-butylphenylboronic acid 3c (84 mg, 0.47 mmol),

Pd(PPh3)4 (23 mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and

1,4-dioxane (5 mL), 4c was isolated as a light yellow solid (80

0:��# @�%�reaction temperature: 90°C for 8 h. Mp.123-125°C. 1H

NMR (300 MHz, CDCl3): � = 1.28 (s, 9H, 3CH3), 1.33 (s, 9H,

3CH3), 7.20 (d, 2H, 8.49 Hz, ArH), 7.28-7.33 (m, 1H, ArH),

7.35-7.40 (m, 3H, ArH), 7.42-7.48 (m, 4H, ArH), 7.54 (d, 2H, J

= 8.6 Hz, ArH), 7.66 (d, 1H, J = 1.89 Hz, ArH), 8.27 (d, 1H, J = 7.80 Hz, ArH). 13C NMR

(62.9 MHz, CDCl3): � = 30.3 (CH3), 30.5 (CH3), 33.4, 33.5 (C), 121.9, 123.8, 124.2, 124.9,

125.1 (CH), 125.6 (C), 126.0, 126.7, 128.6, 128.8 (CH), 130.6 (C), 130.7 (CH), 134.7, 134.9,

137.9, 139.5, 142.3, 145.7, 148.3, 151.0 (C), 179.7 (CO). IR (KBr): v = 3389, 3051, 3030, 2952,

2901, 2865 (w), 1638 (s), 1611 (w), 1588 (s), 1556, 1537 (w), 1511 (m), 1475 (w), 1461, 1434

(m), 1416 (w), 1381, 1360 (m), 1317 (w), 1299 (s), 1267 (m), 1231, 1201 (w), 1157,1109 (m),

1175, 1144, 1032, 1014, 961 (w), 924 (m), 890, 867 (w), 822,754 (s), 746 (m), 719 (s), 697,

671, 671, 656, 646, 613 (w), 581 (s), 563, 549, 541 (w) cm−1. GC-MS (EI, 70 eV): m/z

(%) = 476 ([M]+, 64), 475 ([M-H]+, 100), 462 (15), 461 (46). HRMS (ESI): calcd for C33H33OS

[M+H]+: �99 ��9!%��)�34,��99 ��!

1,3-Bis(3,5-dimethylphenyl)-9H-thioxanthen-9-one (4d): Starting with 2 (100 mg, 0.197

mmol), 3,5-dimethylphenylboronic acid 3d (71 mg, 0.47 mmol),

Pd(PPh3)4 (23 mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and 1,4-

dioxane (5 mL), 4d was isolated as a light yellow solid (64 mg,

99@�%�reaction temperature: 90°C for 8 h. Mp.159-161°C. 1H NMR

(300 MHz, CDCl3): � = 2.31 (s, 6H, 2CH3), 2.32 (s, 6H, 2CH3),

6.88 (brs, 2H, ArH), 6.98 (d, 2H, J = 6.39 Hz, ArH), 7.22 (brs, 2H,

ArH), 7.30-7.36 (m, 1H, ArH), 7.40 (d, 1H, J = 1.83 Hz, ArH), 7.48-7.49 (m, 2H, ArH ), 7.66 (d,

1H, J = 1.86 Hz, ArH), 8.27 (d, 1H, J = 7.80 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): � = 20.3

(CH3), 20.5 (CH3), 122.1 (CH), 124.1 (C), 124.2, 124.7 (CH), 125.0 (C), 125.1, 127.6, 128.3,

��

128.7, 129.3, 130.6, 130.7 (CH), 134.9, 136.2, 137.6, 137.7, 138.0, 142.5, 142.6, 145.8 (C),

179.7 (CO). IR (KBr): v = 3269, 3004, 2914, 2854, 2729 (w), 1640 (s), 1601 (m), 1587 (s), 1540

(m), 1503, 1494, 1468 (w), 1432 (m), 1398 (w), 1382, 1373 (m), 1332, 1315 (w), 1300 (s), 1279

(m), 1245, 1204, 1185, 1168 (w), 1150 (m), 1137, 1117, 1100, 1080 (w), 1034 (m), 1011, 966,

940 (w), 912, 889, 875 (m), 842 (s), 813, 806 (m), 769 (w), 752, 744, 719 (s), 703, 697, 692,

672, 651, 643 (m), 603 (w), 591 (m), 569, 540 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 420

([M]+, 54), 419 ([M-H]+, 100), 405 (39). HRMS (ESI): calcd for C29H25OS [M+H]+: �� !%�

found: 421.16300.

1,3-Di-p-tolyl-9H-thioxanthen-9-one (4e): Starting with 2 (100 mg, 0.197 mmol),

4-methylphenylboronic acid 3e (64 mg, 0.47 mmol), Pd(PPh3)4

(23 mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and 1,4-dioxane

(5 mL), 4e was isolated as a ��:$.� 1��)?� 2)��4� ��0:�� #�@�%�


(300 MHz, CDCl3): � = 2.31(s, 3H, CH3), 2.36 (s, 3H, CH3),

7.15-7.19 (m, 6H, ArH), 7.27-7.32 (m, 1H, ArH), 7.39 (d, 1H,

J =1.89 Hz, ArH), 7.44 (d, 1H, J =1.17 Hz, ArH), 7.48 (d, 3H, J = 8.25 Hz, ArH ), 7.63 (d, 1H,

J =1.89 Hz, ArH), 8.27 (dd, 1H, J = 0.78, 8.61 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 20.2

(CH3), 20.4 (CH3), 121.9, 124.2 (CH), 124.9 (C), 125.1, 126.2, 126.8, 127.6, 128.2, 128.7, 128.8

(CH), 130.5 (C), 130.7 (CH), 134.7, 134.9, 135.3, 137.8, 137.9, 139.7, 142.3, 145.7 (C), 179.7

(CO). IR (KBr): v = 3044, 3022, 2952, 2919, 2857 (w), 1631 (s), 1613 (w), 1588 (s), 1556, 1537

(w), 1511 (m), 1462 (w), 1433 (m), 1415, 1380, 1316, 1192 (w), 1256 (m), 1116, 1107, 1075

(m), 1044 (w), 1031 (m), 1017 (w), 983, 961, 945 (w), 923 (s), 888, 877, 848, 837 (w), 811, 803

(s), 787 (m), 768 (w), 757, 748 (s), 725, 717, 675 (m), 659, 649, 631, 612, 586 (w), 568, 536 (m)

cm−1. GC-MS (EI, 70 eV): m/z (%) = 392 ([M]+, 49), 391 ([M-H]+, 100). HRMS (ESI): calcd for

C27H21OS [M+H]+: �'� ��!#!%��)�34,��'� ��!'!

1,3-Bis(4-chlorophenyl)-9H-thioxanthen-9-one (4f): Starting with 2 (100 mg, 0.197 mmol), 4-

chloro phenylboronic acid 3f (73 mg, 0.47 mmol), Pd(PPh3)4 (23

mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and 1,4-dioxane (5

mL), 4f was isolated as a ��:$.�1��)?�2)��4� !�0:��9!@�%�reaction


CDCl3): � = 7.19 (d, 2H, J = 3.72 Hz, ArH), 7.31-7.39 (m, 6H, �

�

��

��

�

�

��

��

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ArH), 7.46-7.54 (m, 4H, ArH), 7.66 (d, 1H, J = 1.66 Hz, ArH), 8.27 (d, 1H, J = 7.88 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 122.6, 124.3 (CH), 125.1 (C), 125.4, 127.1, 127.6, 127.9,

128.2, 128.3, 129.7 (CH), 130.2 (C), 131.1 (CH), 131.9, 134.2, 134.8, 135.9, 138.4, 140.8,

141.3, 144.6 (C), 179.4 (CO). IR (KBr): v = 3064, 3041, 2920, 2851 (w), 1640, 1589 (s), 1537

(w), 1490 (s), 1470 (w), 1434 (m), 1414, 1397, 1375 (w), 1317, 1298 (m), 1284, 1263, 1234,

1186 (w), 1158 (m), 1107 (w), 1090 (s), 1076 (m), 1032, 1031 (w), 1012 (s), 926 (m), 892, 873,

844 (w), 832 (m), 816, 806, 747 (s), 727, 713 (m), 693 (w), 680, 651 (m), 643, 626, 602 (w),

567, 553 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 433 ([M+H]+, 44), 432 ([M]+, 27), 431 ([M-

H]+, 56), 199 (100), 181 (49), 165 (16). HRMS (EI, 70 eV): calcd for C25H14Cl2OS [M]+:

�� !�� '%��)�34,�� !��

1,3-Bis(3-(trifluoromethyl)phenyl)-9H-thioxanthen-9-one (4g): Starting with 2 (100 mg,

0.197 mmol), 3-(trifluoromethyl)phenylboronic acid 3g (89 mg,

0.47 mmol), Pd(PPh3)4 (23 mg, 10 mol%), K3PO4 (125 mg, 0.59

mmol) and 1,4-dioxane (5 mL), 4g was isolated as a light yellow

2)��4� 9�� 0:�� 9�@�%� ��/7.�on temperature: 90°C for 8 h.

Mp.167-169°C. 1H NMR (300 MHz, CDCl3): � = 7.32-7.38 (m,

2H, ArH), 7.42-7.54 (m, 6H, ArH), 7.56-7.62 (m, 1H, ArH), 7.58-7.59 (m, 1H, ArH), 7.73 (d,

1H, J = 1.90 Hz, ArH), 7.77 (d, 1H, J = 7.68 Hz, ArH), 7.83 (brs, 1H, ArH), 8.22-8.26 (m, 1H,

ArH). 19F NMR (282.4 MHz, CDCl3): � = -62.6, -62.3. 13C NMR (62.9 MHz, CDCl3): � = 122.7

(q, JF,C = 3.7 Hz, CH), 122.9 (q, JF,C = 272.5 Hz, CF3), 123.2 (q, JF,C = 272.5 Hz, CF3),123.2 (q,

JF,C = 3.9 Hz, CH), 123.3 (CH), 123.6 (q, JF,C = 3.9 Hz, CH), 124.4 (CH), 124.5 (q, JF,C =

3.9 Hz, CH), 125.4 (C), 125.6, 127.2, 128.0, 128.6, 128.7 (CH), 129.5 (q, JF,C = 32.2 Hz, C-CF3),

129.7 (CH), 130.1 (C), 130.3 (CH), 130.9 (q, JF,C = 32.5 Hz, C-CF3), 131.2 (CH), 134.7, 138.3,

138.7, 141.2, 142.9, 144.4 (C), 179.3 (CO). IR (KBr): v = 3270, 3063, 2959, 2852 (w), 1641 (s),

1615 (w), 1588 (s), 1547, 1496, 1486, 1462, 1455 (w), 1435 (m), 1380 (w), 1326, 1304 (s), 1268,

1251, 1226 (m), 1195 (w), 1174 (m), 1154, 1112, 1095, 1069, 1052 (s), 1033, 1000, 961, 928,

897, 887, 871, 859 (m), 797, 755 (s), 748 (m), 720, 698 (m), 686, 672, 654 (s), 627, 611, 562,

542 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 500 ([M]+, 45), 499 ([M-H]+, 100), 356 (19), 277

(07), 240 (08). HRMS (EI, 70 eV): calcd for C27H13F6OS [M-H]+,� �'' !�#�#%� �)�34,�

499.058160.

��

Synthesis of 3-Aryl-1-(trifluorosulfonyloxy)-thioxanthones 5a-h:

3-(4-Methoxyphenyl)-9-oxo-9H-thioxanthen-1-yl trifluoromethanesulfonate (5a): Starting

with 2 (100 mg, 0.197 mmol), 4-methoxyphenylboronic acid

3h (33 mg, 0.22 mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4

(63 mg, 0.29 mmol) and THF (5 mL), 5a was isolated as a light

1��)?�2)��4�#!�0:��#9@�%��/7.�)3�.�06��/.��,� !"��)��#�$ �

Mp.186-188°C. 1H NMR (300 MHz, CDCl3): � = 3.81 (s, 3H, OCH3), 6.96 (d, 2H, J = 8.85 Hz,

ArH), 7.33 (d, 1H, J = 1.10 Hz, ArH), 7.41-7.58 (m, 5H, ArH), 7.64 (d, 1H, J = 1.74 Hz, ArH),

8.53 (dd, 1H, J = 1.10, 8.2 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -73.4. 13C NMR

(75.5 MHz, CDCl3): � = 55.5 (OCH3), 114.9 (CH), 118.9 (q, JF,C = 321.3 Hz, CF3), 119.1 (CH),

120.3 (C), 123.4, 125.4, 126.9, 128.5 (CH), 129.2 (C), 130.1 (CH), 130.2 (C), 132.6 (CH), 135.3,

141.0, 145.4, 150.4, 161.0 (C), 178.5 (CO). IR (KBr): v = 3082, 3063, 2841, 1651 (w), 1635,

1594 (s), 1558 (w), 1523 (m), 1471, 1460 (w), 1435 (m), 1425 (s), 1404 (w), 1389 (m), 1328,

1317, 1307 (w), 1286, 1256, 1242, 1219 (m), 1191 (s),1135, 1126, 1111(m), 1060 (w), 1030 (m),

1007 (w), 958, 904, 889, 881 (m), 848 (w), 832 (s), 811, 799 (m), 782, 759 (w), 745 (s), 725 (w),

712, 661, 653, 637 (m), 595 (s), 582, 567, 527 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 466

([M]+, 100), 334 (13), 305 (44), 262 (17). HRMS (EI, 70 eV): calcd for C21H13F3O5S2 [M]+:

� !��!%��)�34,�� !��'

3-(4-Ethylphenyl)-9-oxo-9H-thioxanthen-1-yl trifluoromethanesulfonate (5b): Starting with

2 (100 mg, 0.197 mmol), 4-ethylphenylboronic acid 3b (32 mg,


mmol) and THF (5 mL), 5b was isolated as a yellow solid (77

mg, #�@�%� reaction temperature: 60°C for 8 h. Mp.158-160°C

(CH2Cl2/EtOH 1:1). 1H NMR (300 MHz, CDCl3): � = 1.21 (t, 3H, J =7.59 Hz, CH3), 2.65 (q, 2H,

J =7.59 Hz, CH2), 7.27 (d, 2H, J = 8.32 Hz, ArH), 7.35 (d, 1H, J = 0.96 Hz, ArH), 7.38-7.44 (m,

2H, ArH), 7.46 (d, 2H, J = 8.32 Hz, ArH), 7.50-7.56 (m, 1H, ArH), 7.66 (d, 1H, J = 1.74 Hz,

ArH), 8.52 (dd, 1H, J = 1.05, 8.13 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -73.4. 13C

NMR (62.9 MHz, CDCl3): � = 14.4 (CH3), 27.6 (CH2), 117.4 (q, JF,C = 321.1 Hz, CF3), 118.4

(CH), 120.4 (C), 122.9, 124.4, 125.9, 126.1, 127.9, 129.0 (CH), 129.1 (C), 131.6 (CH), 133.5,

134.3, 139.9, 144.8, 145.3, 149.3 (C), 177.5 (CO). IR (KBr): v = 3052, 2960, 2929, 2871 (w),

1641, 1602, 1589 (s), 1524 (m), 1454, 1444 (w), 1422 (s), 1386, 1316, 1303, 1240 (m), 1221,

1186 (s), 1157 (w), 1134, 1123 (s), 1110 (m), 1080, 1060, 1033, 1018 (w), 955, 899 (s), 862

��

(w), 839 (m), 811, 798 (s), 759 (w), 745 (s), 714 (m), 666, 659, 637 (w), 595, 577, 569 (s), 531

(w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 464 ([M]+, 100), 332 (14), 303 (39), 275 (17), 260

(19). HRMS (EI, 70 eV): calcd for C22H15F3O4S2 [M]+,�� !��#�%��)�34,�� !��'!

3-(4-(Tert-butyl)phenyl)-9-oxo-9H-thioxanthen-1-yl trifluoromethanesulfonate (5c): Starting

with 2 (100 mg, 0.197 mmol), 4-tert-butyl phenylboronic acid 3c

(39 mg, 0.22 mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg,

0.29 mmol) and THF (5 mL), 5c was isolated as a yellow solid

9��0:��9�@�%�reaction temperature: 60°C for 8 h. Mp.170-172°C

(CH2Cl2/EtOH 1:1). 1H NMR (300 MHz, CDCl3): � = 1.30 (s, 9H,

3CH3), 7.36 (d, 1H, J = 0.90 Hz, ArH), 7.38-7.46 (m, 2H, ArH), 7.48-7.57 (m, 5H, ArH), 7.68

(d, 1H, J = 1.68 Hz, ArH), 8.52 (dd, 1H, J =1.08, 8.10 Hz, ArH). 19F NMR (282.4 MHz, CDCl3):

� = -73.4. 13C NMR (75.5 MHz, CDCl3): � = 31.2 (CH3), 31.9 (C), 118.9 (q, JF,C = 321.0 Hz,

CF3), 119.5 (CH), 120.7 (C), 124.0, 125.4, 126.4, 126.9, 130.1 (CH), 130.2 (C), 132.7 (CH),

134.1, 135.3, 141.0, 145.8, 150.4, 153.2 (C), 178.6 (CO). IR (KBr): v = 3087, 3050, 3022, 2966,

2920, 2872, 2854 (w), 1630, 1602, 1589 (s), 1524 (m), 1480 (w), 1465, 1437 (m), 1424 (s), 1384

(m), 1362, 1325 (w), 1305 (m), 1278 (w), 1241 (m), 1217, 1193 (s), 1171 (m), 1131, 1105 (s),

1078, 1059, 1035, 1024, 1014 (w), 958, 903 (s), 890 (m), 829 (s), 810 (m), 801 (s), 760 (m), 753

(s), 712 (m), 666, 658, 651, 637 (w), 588 (s), 568, 537, 529 (w) cm−1. GC-MS (EI, 70 eV): m/z

(%) = 493 ([M+H]+, 17), 492 ([M]+, 59), 478 (28), 477 (100), 316 (36). HRMS (EI, 70 eV):

calcd for C24H19F3O4S2 [M]+,��'� ! 9��%��)�34,��'� ! ��

3-(3,5-Dimethylphenyl)-9-oxo-9H-thioxanthen-1-yl trifluoromethanesulfonate (5d): Starting

with 2 (100 mg, 0.197 mmol), 3,5-dimethylphenylboronic acid 3d

(33 mg, 0.22 mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg,

0.29 mmol) and THF (5 mL), 5d was isolated as a yellow solid (75

0:�� #�@�%� reaction temperature: 60°C for 8 h. Mp.221-223°C. 1H

NMR (300 MHz, CDCl3): � = 2.34 (s, 6H, 2CH3), 7.04 (brs, 1H,

ArH), 7.14 (brs, 2H, ArH), 7.35 (d, 1H, J = 0.96 Hz, ArH), 7.39-7.48 (m, 2H, ArH), 7.52-7.58

(m, 1H, ArH), 7.67 (d, 1H, J =1.71 Hz, ArH), 8.53 (dd, 1H, J =1.02, 7.68 Hz, ArH). 19F NMR

(282.4 MHz, CDCl3): � = -73.4. 13C NMR (75.5 MHz, CDCl3): � = 20.4 (CH3), 117.9 (q, JF,C =

321.1 Hz, CF3), 118.7 (CH), 119.7 (C), 123.3, 124.0, 124.4, 125.9, 129.1 (CH), 129.2 (C), 130.3,

131.6 (CH), 134.3, 136.0, 138.1, 139.9, 145.2, 149.2 (C), 177.6 (CO). IR (KBr): v = 3152, 3115,

�

� ��

�

� ��

��

3059, 2951, 2917, 2849 (w), 1631, 1601, 1588 (s), 1555 (w), 1534 (m), 1503, 1483 (w), 1427 (s),

1408 (w), 1375, 1302 , 1248 (m), 1217, 1197, 1186, 1130 (s), 1081 (m) , 1031, 1004 (w), 964,

911 (m), 894, 888 (s), 871 (m), 842, 813, 803 (s), 760 (w), 727 (w), 715, 686, 660 (m), 630 (w),

609 (m), 589 (s), 568 (m), 545, 537 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 464 ([M]+, 100),

303 (46), 275 (27). HRMS (EI, 70 eV): calcd for C22H15F3O4S2 [M]+,� � � !��#�%� �)�34,�

464.03623.

9-Oxo-3-phenyl-9H-thioxanthen-1-yl trifluoromethanesulfonate (5e): Starting with 2 (100

mg, 0.197 mmol), phenylboronic acid 3i (26 mg, 0.22 mmol),

Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg, 0.29 mmol) and THF (5

mL), 5e was isolated as a 1��)?� 2)��4� �� 0:�� 9�@�%� reaction


CDCl3): � = 7.36 (d, 1H, J = 0.87 Hz, ArH), 7.39-7.47 (m, 5H, ArH), 7.50-7.56 (m, 3H, ArH),

7.67 (d, 1H, J = 1.68 Hz, ArH), 8.50 (dd, 1H, J = 1.11, 8.16 Hz, ArH). 19F NMR (282.4 MHz,

CDCl3): � = -73.3. 13C NMR (75.5 MHz, CDCl3): � = 118.9 (q, JF,C = 321.0 Hz, CF3), 119.6

(CH), 120.9 (C), 124.3, 125.4, 127.0, 127.2, 129.4, 129.7, 130.0 (CH), 130.1 (C), 132.7 (CH),

135.3, 137.0, 141.1, 145.8, 150.4 (C), 178.5 (CO). IR (KBr): v = 3083, 3062, 3023, 2917, 2848

(w), 1635, 1606, 1588 (s), 1531 (m), 1506, 1463, 1448 (w), 1423 (s), 1404 (w), 1388 (m), 1345,

1321 (w), 1306 (m), 1277 (w), 1242, 1218 (m), 1189 (s), 1169, 1157 (m), 1135, 1124, 1109 (s),

1081, 1032 (m), 999 (w), 956, 902, 876 (s), 843 (w), 810, 802, 761, 748 (s), 716, 684, 673, 666

(m), 622 (w), 637 (w), 597, 585 (s), 568 (m), 530 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 436

([M]+, 100), 275 (49), 247 (48), 245 (16). HRMS (ESI): calcd for C20H12F3O4S2 [M+H]+:

��9 !��!%��)�34,��9 !��#!

3-(4-Chlorophenyl)-9-oxo-9H-thioxanthen-1-yl trifluoromethanesulfonate (5f): Starting with

2 (100 mg, 0.197 mmol), 4-chlorophenylboronic acid 3f (34 mg,


mmol) and THF (5 mL), 5f was isolated as a yellow solid (72

0:�� 9#@�%� reaction temperature: 60°C for 8 h. Mp.133-135°C. 1H NMR (300 MHz, CDCl3): � = 7.34 (d, 1H, J = 0.80 Hz, ArH),

7.42-7.51 (m, 6H, ArH), 7.57 (d, 1H, J = 8.25 Hz, ArH), 7.67 (d, 1H, J = 1.67 Hz, ArH), 8.45

(dd, 1H, J = 1.01, 7.95 Hz, ArH). 19F NMR (282.4 MHz,CDCl3): � = -73.3. 13C NMR

(75.5 MHz, CDCl3): � = 118.7 (q, JF,C = 321.1 Hz, CF3), 119.5 (CH), 121.1 (C), 124.2, 125.4,

127.1, 128.5 (CH), 129.6 (C), 129.7, 130.2, 132.8 (CH), 135.2, 135.5, 136.1, 141.2, 144.5, 150.4

��

(C), 178.5 (CO). IR (KBr): v = 3087, 3060, 3023, 2956, 2918, 2849 (w), 1714, 1673, 1668 (w),

1639, 1606, 1590 (s), 1531 (w), 1503 (m), 1463, 1456 (w), 1426 (s), 1380 (m), 1319 (w), 1303

(m), 1276, 1262 (w), 1242 (m), 1219, 1190 (s), 1167, 1159 (w), 1135, 1126 (s), 1112 (w), 1090

(s), 1049, 1033 (w), 1010 (m), 955 (s), 928 (w), 902, 890 (s), 845 (w), 832 (m), 811, 799 (s), 760

(m), 748 (s), 717, 712 (m), 692 (w), 666, 659, 654, 630 (m), 595, 586 (s), 567 (m), 558, 537 (w)

cm−1. GC-MS (EI, 70 eV): m/z (%) = 470 ([M+H]+, 100), 338 (11), 311 (19), 310 (12), 309 (47),

281 (41), 274 (12), 245 (22). HRMS (ESI): calcd for C20H11F3ClO4S2 [M+H]+,� �9! '9��!%�

found: 470.97450.

9-Oxo-3-(3-(trifluoromethyl)phenyl)-9H-thioxanthen-1-yl trifluoromethanesulfonate (5g):

Starting with 2 (100 mg, 0.197 mmol), 3-

(trifluoromethyl)phenylboronic acid 3g (41 mg, 0.22 mmol),

Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg, 0.29 mmol) and THF

(5 mL), 5g ?/2��2)�/.�4�/2�/�1��)?�2)��4�#!�0:��#�@�%�reaction

temperature: 60°C for 8 h. Mp.176-177°C. 1H NMR (300 MHz, CDCl3): � = 7.35 (d, 1H,

J = 1.14 Hz, ArH), 7.40-7.48 (m, 2H, ArH), 7.54-7.62 (m, 2H, ArH), 7.67-7.74 (m, 3H, ArH),

7.77 (brs, 1H, ArH), 8.52 (dd, 1H, J = 1.11, 8.16 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -

73.3, -62.7. 13C NMR (62.9 MHz, CDCl3): � = 118.9 (q, JF,C = 323.9 Hz, CF3), 119.7 (CH),

121.4 (C), 123.7 (q, JF,C = 272.5 Hz, CF3), 124.0 (q, JF,C = 3.79 Hz, CH), 124.6, 125.4 (CH),

126.3 (q, JF,C = 3.66 Hz, CH), 127.2, 130.0 (CH), 130.1 (C), 130.2, 130.6 (CH), 131.9 (q, JF,C =

32.5 Hz, C-CF3), 132.9 (CH), 135.1, 137.9, 141.4, 144.2, 150.4 (C), 178.4 (CO). IR (KBr): v =

3083, 3062, 3023, 2918, 2851 (w), 1630, 1609, 1589 (s), 1537, 1502, 1461 (w), 1424 (s), 1386

(m), 1336 (s), 1303, 1267, 1240, 1224 (m), 1204 (s), 1166 (m), 1123 (s), 1078, 1066 (m), 1033,

1000 (w), 963 (s), 906, 877 (m), 814, 801 (s), 777 (w), 761, 750 (m), 734 (w), 717, 661 (m), 685

(s), 566, 657, 647, 633, 623 (w), 595 (s), 568 (m), 533 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) =

503 ([M]+, 46), 375 (42), 311 (100), 283 (15), 242 (27), 214 (16), 186 (29), 158 (13). HRMS

(EI, 70 eV): calcd for C21H10F6O4S2 [M]+,��!� ''�'�%��)�34,��!� ''��# ��

3-(4-Fluorophenyl)-9-oxo-9H-thioxanthen-1-yl trifluoromethanesulfonate (5h): Starting with

2 (100 mg, 0.197 mmol), 4-flourophenylboronic acid 3j (30 mg,


mmol) and THF (5 mL), 5h was isolated as a yellow solid (71 mg,

#!@�%� reaction temperature: 60°C for 8 h. Mp.179-181°C. 1H

��

NMR (300 MHz, CDCl3): � = 7.13 (t, 2H, J = 8.52 Hz ArH), 7.30 (d, 1H, J = 1.02 Hz, ArH),

7.38-7.45 (m, 2H, ArH), 7.49-7.58 (m, 3H, ArH), 7.63 (d, 1H, J = 1.74 Hz, ArH), 8.50 (dd, 1H,

J = 0.90, 7.80 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -111.1, -73.3. 13C NMR (75.5 MHz,

CDCl3): � = 116.5 (d, JF,C = 21.9 Hz, CH), 118.9 (q, JF,C = 321.2 Hz, CF3), 119.5 (CH), 120.9

(C), 124.1, 125.4, 127.0 (CH), 129.1 (d, JF,C = 8.46 Hz, CH), 130.1, 132.8 (CH), 133.1, 133.2,

135.2, 141.2, 144.7, 150.4 (C), 163.8 (d, JF,C = 250.9 Hz, C-F), 178.8 (CO). IR (KBr): v = 3070,

2953, 2921, 2851 (w), 1637(m), 1591 (s), 1531 (w), 1514 (m), 1488, 1435 (w), 1421 (s), 1383

(m), 1321 (w), 1302 (m), 1281 (w), 1241(m), 1207, 1191 (s), 1163 (m), 1137, 1116 (s), 1079 (m)

, 1034, 1014, 993 (w), 957, 903 (s), 876 (m), 854 (w), 838, 810, 792, 754, 741 (s), 715, 665, 659

(m), 636 (w), 590 (s), 569 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 454 ([M]+, 100), 294 (10),

293 (49), 265 (52), 263 (14). HRMS (ESI): calcd for C20H11F4O4S2 [M+H]+,�� !!�'!%��)�34,�

455.00300.

Synthesis of unsymmetrical diarylthioxanthones 6a-d:

General procedure (A) for Suzuki cross-coupling reactions: The reaction was carried out in a

pressure tube. To a THF suspension (4-5 mL) of 1,3-bis(triflates) 2 (100 mg, 0.197 mmol),

Pd(PPh3)4 (5 mol%) and of the Ar1B(OH)2 (1.1 equiv.), K3PO4 (1.5 equiv.) was added. The

mixture was heated at the indicated temperature (60°C) under Argon atmosphere for the

indicated period of time (8 h) and cooled to room temperature, then diluted with water and

extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were dried (Na2SO4), filtered

and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography

silica gel (EtOAc/ heptanes). Then to a 1,4-dioxane (4-5 mL) suspension of products 5 (b,c,f),


reaction mixture was further heated at (90°C) for (6 h). The reaction mixture was again cooled to

room temperature and diluted with water and extracted with CH2Cl2 (3 x 25 mL). The combined

organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The

residue was purified by flash chromatography (silica gel, EtOAc/ heptanes).

General procedure (B) for Suzuki cross-coupling reactions: The reaction was carried out in a

pressure tube. To a THF suspension (4-5 mL) of 1,3-bis(triflates) 2 (100 mg, 0.197 mmol),


mixture was heated at the indicated temperature (60°C) under Argon atmosphere for the

indicated period of time (8 h) and cooled to room temperature, then Ar2B(OH)2 (1.1 equiv.) was

��

added, the reaction mixture was further heated at (90°C) for (6 h). The reaction mixture was

again cooled to room temperature and diluted with water and extracted with CH2Cl2 (3 x 25 mL).

The combined organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in

vacuo. The residue was purified by flash chromatography (silica gel, EtOAc/ heptanes).

3-(4-Ethylphenyl)-1-(2-methoxyphenyl)-9H-thioxanthen-9-one (6a): Starting with 5b (77 mg,

0.166 mmol), 2-methoxyphenylboronic acid 3a (28 mg, 0.182

mmol), (10 mg, 5 mol%) K3PO4 (53 mg, 0.25 mmol) and 1,4-

dioxane (5 mL), following the general procedure A, 6a was isolated

as a 1��)?�2)��4��9�0:��#�@�%�reaction temperature: 90°C for 6 h.

Mp.185-187°C. 1H NMR (300 MHz, CDCl3): � = 1.20 (t, 3H,

J = 7.59 Hz CH3), 2.63 (s, 2H, J =7.59 Hz, CH2), 3.58 (s, 3H,

OCH3), 6.88 (dd, 1H, J = 0.66, 8.19 Hz, ArH), 7.02 (td, 1H, J = 1.02, 7.44 Hz, ArH), 7.23 (d,

3H, J = 7.68 Hz, ArH), 7.28-7.35 (m, 2H, ArH), 7.42 (d, 1H, J = 1.86 Hz, ArH), 7.46-7.48 (m,

2H, ArH), 7.53 (d, 2H, J = 8.25 Hz, ArH), 7.66 (d, 1H, J = 1.86 Hz, ArH), 8.23 (dt, 1H, J = 0.96,

8.10 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): � = 15.5 (CH3), 28.6 (CH2), 55.5 (OCH3), 110.3,

120.7, 123.2, 125.3, 126.1 (CH), 127.0 (C), 127.3, 128.5, 128.9, 129.1, 129.4, 131.4, 131.5

(CH), 132.7, 136.0, 136.2, 138.0, 142.2, 143.7, 144.9, 156.0 (C), 180.9 (CO). IR (KBr): v =

3272, 3109, 3061, 3012, 2964, 2865, 2238, 1922, 1899 (w), 1643, 1589 (s), 1538, 1514, 1494,

1461, 1452, 1435 (m), 1385 (w), 1301 (s), 1278 (m), 1241 (s), 1228, 1189, 1180 (w), 1156,

1117, 1074, 1052 (m), 1032 (w), 1020 (s), 964, 938 (w), 925 (m), 896, 871, 838 (w), 826 (s),

802(m), 769 (w), 751, 741, 719 (s), 677, 660 (m), 647, 636, 629, 623, 593, 577, 552 (w), 536 (m)

cm−1.GC-MS (EI, 70 eV): m/z (%) = 422 ([M]+, 4), 391 ([M]+, 100), 376 (65). HRMS (EI,

70 eV): calcd for C28H22O2S [M]+: �� !%��)�34,��

3-(4-(Tert-butyl)phenyl)-1-(4-methoxyphenyl)-9H-thioxanthen-9-one (6b): Starting with 5c

(73 mg, 0.148 mmol), 4-methoxyphenylboronic acid 3h (25 mg,


mmol) and 1,4-dioxane (5 mL), following the general procedure

A, 6b was isolated as a 1��)?� 2)��4� �� 0:�� 9'@�%� reaction

temperature: 90°C for 6 h. Mp.178-180°C (CH2Cl2/EtOH 1:1). 1H

NMR (300 MHz, CDCl3): � = 1.28 (s, 9H, 3CH3), 3.79 (s, 3H,

OCH3), 6.89 (d, 2H, J = 8.70 Hz, ArH), 7.19 (d, 2H, J = 8.70 Hz,

�

�

��

��

ArH), 7.29-7.34 (m, 1H, ArH), 7.40-7.48 (m, 5H, ArH), 7.54 (d, 2H, J = 8.52 Hz, ArH), 7.65 (d,

1H, J = 1.83 Hz, ArH), 8.27 (dd, 1H, J = 0.75, 8.52 Hz, ArH). 13C NMR (62.9 MHz, CDCl3):

� = 31.3 (CH3), 34.7 (C), 55.2 (OCH3), 113.4, 122.9, 125.2 (CH), 125.9 (C), 126.0, 126.2, 127.0,

129.1, 129.4, 129.7 (CH), 131.6 (C), 131.7 (CH), 135.7, 135.8, 136.0, 139.0, 143.0, 146.0, 152.0,

158.6 (C), 180.9 (CO). IR (KBr): v = 3092, 3051, 3005, 2950, 2902, 2865, 2830 (w), 1642 (s),

1607 (m), 1587 (s), 1557, 1537 (w), 1507 (s), 1460, 1432 (m), 1415, 1379, 1359, 1316 (w), 1297

(s), 1279 (m), 1238 (s), 1176 (m), 1163 (w), 1152, 1111, 1074, 1028 (m), 1015, 961 (w), 923

(m), 891, 867 (w), 818 (s), 769 (w), 754 (s), 730, 722 (m), 709 (w), 675 (m), 653, 633, 611 (w),

573, 542 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 450 ([M]+, 77), 449 ([M-H]+, 100). HRMS

(ESI): calcd for C30H27O2S [M+H]+: �� 9� !%��)�34,�� 9��!

3-(4-Chlorophenyl)-1-(3,4-dimethoxyphenyl)-9H-thioxanthen-9-one (6c): Starting with 5f (72

mg, 0.153 mmol), 3,4-dimethoxyphenylboronic acid 3k (31 mg,


mmol) and 1,4-dioxane (5 mL), following the general procedure A,

6c was isolated as a 1��)?� 2)��4� �!� 0:�� 9�@�%� ��/7.�)3�


CDCl3): � = 3.79 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 6.77 (d, 1H,

J = 1.86 Hz, ArH), 6.81 (dd, 1H, J = 1.92, 8.16 Hz, ArH), 6.88 (d, 1H, J = 8.16 Hz, ArH), 7.32-

7.39 (m, 4H, ArH), 7.48-7.55 (m, 4H, ArH), 7.62 (d, 1H, J = 1.9 Hz, ArH), 8.25 (dd, 1H, J =

0.84, 8.70 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): � = 54.8, 54.9 (OCH3), 109.7, 110.7, 119.1,

122.0, 124.3, 125.4, 127.6, 128.1, 128.3, 128.6 (CH), 130.7 (C), 130.9 (CH), 134.0, 134.7, 134.8,

136.1, 138.1, 141.1, 145.5, 147.2, 147.5 (C), 179.8 (CO). IR (KBr): v = 3052, 2989, 2957, 2925,

2850, 2829, 2247 (w), 1643 (s), 1609 (w), 1589 (m), 1537(w), 1513, 1491, 1469, 1462, 1454,

1434, 1417 (m), 1401, 1372, 1331 (w), 1296 (m), 1281 (w), 1257, 1240, 1216, 1185, 1170, 1153,

1136, 1122, 1102, 1092, 1077, 1056 (m), 1027, 1013 (s), 952, 932 (w), 909, 894, 875, 863 (m),

841 (w), 825 (m), 816 (s), 804, 789, 761 (m), 747, 721 (s), 683, 662, 652, 646, 629, 618, 600,

583, 541 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 458 ([M]+, 100), 457 ([M-H]+, 74), 443 (24),

371 (17), 214 (14). HRMS (EI, 70 eV): calcd for C27H19ClO3S [M]+: ��# !9�9'%� �)�34,�

458.074006.

��

1-(4-Methoxyphenyl)-3-(o-tolyl)-9H-thioxanthen-9-one (6d): Starting with 2 (100 mg, 0.197

mmol), 2-methylphenylboronic acid 3l (29 mg, 0.22 mmol), 4-

methoxyphenylboronic acid 3h (34 mg, 0.22 mmol), Pd(PPh3)4 (23

mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and 1,4-dioxane (5 mL),

following the general procedure B, 6d was isolated as a yellow solid

!�0:��9�@�%�reaction temperature: at 60°C for 8 h, at 90°C for 6 h.

Mp.168-170°C. 1H NMR (300 MHz, CDCl3): � = 2.37 (s, 3H, CH3),

3.77 (s, 3H, OCH3), 6.88 (d, 2H, J = 8.73 Hz, ArH), 7.17-7.23 (m, 7H, ArH), 7.31-7.36 (m, 1H,

ArH), 7.42 (d, 1H, J =1.74 Hz, ArH), 7.47-7.52 (m, 2H, ArH), 8.28 (dd, 1H, J = 0.84, 8.64 Hz,

ArH). 13C NMR (75.5 MHz, CDCl3): � = 20.4 (CH3), 55.2 (OCH3), 113.4, 125.2, 125.4 (CH),

125.9 (C), 126.1, 126.3, 128.3, 129.2, 129.5, 129.7, 130.7 (CH), 131.7 (C), 131.8, 131.9 (CH),

135.3, 135.5, 135.9, 138.4, 139.6, 144.8, 145.6, 158.6 (C), 181.2 (CO). IR (KBr): v = 3399,

3057, 2950, 2928, 2861, 2834 (w), 1641 (s), 1607 (m), 1588 (s), 1536(w), 1508 (s), 1489, 1461

(w), 1435 (m), 1409, 1384, 1316 (w), 1295 (m), 1241 (s), 1175, 1156 (m), 1115, 1077, 1053 (w),

1032 (m), 962 (w), 923 (m), 879, 894(w), 826 (s), 808, 786, 769 (w), 755, 723 (s), 680, 667 (m),

643, 613 (w), 573 (m), 556, 536 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 408 ([M]+, 70), 407

([M-H]+, 100). HRMS (EI, 70 eV): calcd for C27H20O2S [M]+: �!# ��9#�%��)�34,��!# ��

Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of the Bis(triflate) of 1,4-

Dihydroxythioxanthone�

Synthesis of� 9-oxo-9H-thioxanthene-1,4-diyl bis(trifluoromethanesulfonate) (8): To a

solution of 7 (0.40 g, 1.63 mmol) in CH2Cl2 (20 mL) was added a

mixture base from Et3N and pyridine 1:2 (0.34 mL, 2.46 mmol of Et3N

and 0.40 mL, 4.10 mmol of pyridine), at 20 °C under an argon

atmosphere. After stirring for 10 min at -78°C, Tf2O (0.66 mL,

3.91mmol) was added. The mixture was allowed to warm to 20°C and stirred for further 8 h. The

reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was

chromatographed without work up (flash silica gel, heptanes-EtOAc) and 8 was isolated as a

yellow solid (0.72 g, 86.7%), Mp.140-142°C. 1H NMR (300 MHz, CDCl3): � = 7.29 (d, 1H, J =

8.91 Hz, ArH), 7.48-7.58 (m, 2H, ArH), 7.62-7.67 (m, 2H, ArH), 8.50 (dd, 1H, J = 1.41,

8.10 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -73.2, -73.9. 13C NMR (62.9 MHz, CDCl3):

� = 118.5, 118.7 (q, JF,C = 317.6, 321.0 Hz, CF3), 120.9 (CH), 124.2 (C), 124.8, 126.1, 128.0

(CH), 129.5 (C), 130.2 (CH), 133.2 (C), 133.5 (CH), 135.2, 143.4, 148.7 (C), 178.0 (CO). IR

��

(KBr): v = 3080, 2961, 2904 (w), 1649, 1592 (w), 1429 (m), 1412, 1388, 1318, 1302 (w), 1257

(s), 1236, 1216, 1199 (m), 1078, 1010 (s), 907, 882, 850 (m), 789, 758 (s), 740 (m), 691, 673,

660, 646, 620, 607 (w), 589 (m), 569, 529 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 508

([M+H]+, 43), 375 (40), 311 (100), 311 (100), 283 (14), 242 (27). HRMS (EI, 70 eV): calcd for

C15H6F6O7S3 [M]+,��!9 '�9��%��)�34,��!9 '�9''

General procedure for Suzuki–Miyaura cross-coupling reactions: A THF solution (4-5 mL),

K3PO4 (1.5 equiv. per cross-coupling), Pd(PPh3)4 (5 mol% per cross-coupling) and arylboronic

acid 3 (1.1 equiv. per cross-coupling) was stirred at 65-90°C for 8 h. After cooling to 20°C,

distilled H2O was added. The organic and the aqueous layers were separated and the latter was

extracted with CH2Cl2. The combined organic layers were dried (Na2SO4), filtered and the

filtrate was concentrated in vacuo. The residue was purified by column chromatography (flash

silica gel, heptanes-EtOAc).

Synthesis of 1,4-diarylthioxanthones 9a-f :

1,4-Bis(4-ethylphenyl)-9H-thioxanthen-9-one (9a): Starting with 8 (100 mg, 0.197 mmol), 4-

ethylphenylboronic acid 3b (71 mg, 0.47 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 9a was isolated as a

1��)?� 2)��4� � � 0:�� #!@�%� reaction temperature: 90°C for 8 h. Mp.130-

132°C. 1H NMR (300 MHz, CDCl3): � = 1.25-1.31 (m, 6H, 2CH3), 2.64-2.75

(m, 4H, 2CH2), 7.12-7.18 (m, 2H, ArH), 7.21-7.31 (m, 5H, ArH ), 7.33-7.47

(m, 6H, ArH), 8.19 (dd, 1H, J = 1.20, 8.19 Hz, ArH). 13C NMR (75.5 MHz,

CDCl3): � = 14.2, 14.4 (2CH3), 27.6, 27.7 (2CH2), 124.5, 125.1 (CH), 125.9

(C), 126.5, 126.9, 127.1, 128.2, 128.6, 128.8 (CH), 130.2 (C), 130.6, 131.0

(CH), 134.8, 135.4, 136.5, 137.7, 139.7, 141.4, 143.7, 143.8 (C), 181.2 (CO) . IR (KBr): v =

3270, 3053, 3024, 2961, 2929, 2872 (w), 1730 (m), 1642 (s), 1610 (w), 1589 (m), 1547, 1511,

1494, 1474, 1462 (w), 1433 (s), 1408, 1377, 1358 (w), 1304, 1273, 1250, 1215 (m), 1184, 1160,

1137, 1115 (w), 1080, 1072 (m), 1045, 1027 (w), 1013 (m), 970, 934, 886 (w), 822,757, 734 (s),

717, 690 (m), 651 (w), 640 (m), 612, 602 (w), 534 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 420

([M]+, 61), 419 ([M-H]+, 100), 404 (12), 391 (13). HRMS (EI, 70 eV): calcd for C29H23OS [M-

H]+,��' �� %��)�34,��' ��9�

��

1,4-Bis(4-(tert-butyl)phenyl)-9H-thioxanthen-9-one (9b): Starting with 8 (100 mg, 0.197

mmol), 4-tert-butylphenylboronic acid 3c (84 mg, 0.47 mmol), Pd(PPh3)4 (23

mg, 10 mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 9b was isolated

as a 1��)?�2)��4�9#�0:��#�@�%�reaction temperature: 90°C for 8 h. Mp.108-

110°C. 1H NMR (300 MHz, CDCl3): � = 1.33 (s, 9H, 3CH3), 1.35 (s, 9H,

3CH3), 7.20-7.31 (m, 3H, ArH), 7.35-7.45 (m, 8H, ArH), 7.47 (d, 2H, J =

8.29 Hz, ArH), 8.20 (dd, 1H, J = 1.17, 9.57 Hz, ArH). 13C NMR (75.5 MHz,

CDCl3): � = 30.4, 30.5 (CH3), 33.5, 33.8 (C), 123.9, 124.4, 124.6, 125.0,

126.6 (CH), 127.1 (C), 128.1, 128.2, 128.9 (CH), 130.2 (C), 130.6, 131.0

(CH), 134.6, 135.4, 136.4, 137.6, 139.4, 143.7, 148.2, 150.5 (C), 181.2 (CO.

IR (KBr): v = 3025, 2959, 2902, 2866, 2712, 2257, 1909, 1726 (w), 1638 (s), 1614 (w), 1589

(m), 1563, 1543 (w), 1509, 1461 (m), 1433 (s), 1392, 1360 (w), 1308 (m), 1289 (w), 1267, 1256

(m), 1237 (w), 1212, 1203 (m), 1168, 1161, 1138 (w), 1112 (m), 1105, 1080, 1047, 1025 (w),

1014 (m), 973, 961, 935 (w), 917, 905, 847 (m), 835 (w), 821 (s), 801, 759, 748 (m), 724 (s),

700, 687, 666 (w), 648 (m), 625, 611, 604, 590 (w), 568 (s) cm−1. GC-MS (EI, 70 eV): m/z (%) =

476 ([M]+, 81), 475 ([M-H]+, 100), 461 (51), 419 (14). HRMS (EI, 70 eV): calcd for C33H31OS

[M-H]+,��9� �!'!�%��)�34,��9� �!#99

1,4-Di-p-tolyl-9H-thioxanthen-9-one (9c): Starting with 8 (100 mg, 0.197 mmol), 4-

methylphenylboronic acid 3e (64 mg, 0.47 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 9c was isolated as a

1��)?� 2)��4� �� 0:�� #�@�%� reaction temperature: 90°C for 8 h. Mp.160-

162°C. 1H NMR (300 MHz, CDCl3): � = 2.35 (s, 3H, CH3), 2.39 (s, 3H, CH3),

7.14-7.15 (m, 4H, ArH), 7.21-7.32 (m, 6H, ArH), 7.34-7.41 (m, 3H, ArH),

8.18 (dd, 1H, J =1.18, 7.93 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 20.3,

20.4 (2CH3), 124.4, 125.1, 126.8 (CH), 127.1 (C), 127.7, 128.1, 128.4, 128.5,

128.7 (CH), 130.2 (C), 130.6, 130.9 (CH), 134.6, 135.2, 135.4, 136.5, 137.4,

137.7, 139.6, 143.8 (C), 181.1 (CO). IR (KBr): v = 3271, 3027, 2961, 2914, 2859, 2726, 2253

(w), 1642 (s), 1615 (w), 1589 (s), 1574, 1557, 1494, 1547 (w), 1512 (m), 1463 (w), 1434 (s) ,

1378, 1358 (w), 1305 (s), 1285 (w), 1250, 1234, 1204 (m) , 1183, 1159, 1139 (w), 1107 (m) ,

1080, 1070, 1045, 1033 (w), 1016 (m), 971, 956, 934, 917, 896, 864, 848, 838 (w), 805 (s), 773

(w), 758, 736, 728 (s), 688, 661, 650 (w), 642 (m), 627, 621, 613, 601, 585 (w), 556 (m), 544

� ��

(w), 530 (s) cm−1. GC-MS (EI, 70 eV): m/z (%) = 392 ([M]+, 56), 391 ([M-H]+, 100). HRMS

(EI, 70 eV): calcd for C27H19OS [M-H]+,��'� ��%��)�34,��'� ��!'

1,4-Bis(4-methoxyphenyl)-9H-thioxanthen-9-one (9d): Starting with 8 (100 mg, 0.197 mmol),

4-methoxyphenylboronic acid 3h (72 mg, 0.47 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 9d was isolated as a

1��)?� 2)��4� 99� 0:�� '�@�%� reaction temperature: 90°C for 8 h. Mp.193-

194°C. 1H NMR (300 MHz, CDCl3): � = 3.83 (s, 3H, OCH3), 3.84 (s, 3H,

OCH3), 6.89 (d, 2H, J = 8.66 Hz, ArH), 6.98 (d, 2H, J = 8.66 Hz, ArH), 7.16-

7.25 (m, 3H, ArH), 7.28-7.49 (m, 6H, ArH), 8.19 (dd, 1H, J = 1.02, 8.01 Hz,

ArH). 13C NMR (75.5 MHz, CDCl3): � = 55.2, 55.4 (2OCH3), 113.5, 114.0,

125.5, 126.2 (CH), 128.1(C), 129.1, 129.2, 129.8 (CH), 130.8 (C), 130.9

(CH), 131.3 (C), 131.7, 132.1(CH), 135.8, 136.4, 137.8, 138.4, 144.4, 158.5, 159.8 (C), 182.4

(CO) . IR (KBr): v = 3061, 3031, 3004, 2952, 2921, 2852, 2834, 2537, 2350, 2285, 2252, 2052,

1907 (w), 1634, 1606, 1589 (s), 1575 (m), 1556, 1547 (w), 1509 (s), 1462 (m), 1432 (s), 1409,

1377, 1358 (w), 1310, 1302, 1287 (m), 1239 (s), 1193 (m), 1174 (s), 1117 (w), 1105 (m), 1081,

1049 (w), 1026 (s), 1008, 965, 935, 927, 918, 903, 877, 864, 832 (w), 815 (s), 788, 773 (w),

759, 724 (s), 689 (w), 662, 651, 644 (m), 629, 609, 594 (w), 569 (m), 542 (s) cm−1. GC-MS (EI,

70 eV): m/z (%) = 425 ([M+H]+, 51), 424 ([M]+, 99), 423 ([M-H]+, 100), 380 (11). HRMS (EI,

70 eV): calcd for C27H20O3S [M]+: 42� ��99%��)�34,��

1,4-Diphenyl-9H-thioxanthen-9-one (9e): Starting with 8 (100 mg, 0.197 mmol),

phenylboronic acid 3i (57 mg, 0.47 mmol), Pd(PPh3)4 (23 mg, 10 mol%),

K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 9e was isolated as a yellow

solid (65 0:��'�@�%� reaction temperature: 90°C for 8 h. Mp.193-195°C. 1H

NMR (300 MHz, CDCl3): � = 7.27 (t, 4H, J = 7.50 Hz, ArH), 7.31-7.36 (m,

4H, ArH), 7.38-7.47 (m, 7H, ArH), 8.18 (dd, 1H, J = 1.05, 8.04 Hz, ArH). 13C

NMR (75.5 MHz, CDCl3): � = 124.5, 125.2, 125.5, 126.8, 126.9 (CH), 127.0

(C), 127.6, 127.7, 128.2, 128.6, 128.7 (CH), 130.1 (C), 130.7, 130.9 (CH), 135.3, 136.5, 137.5,

137.9, 142.5, 144.0 (C), 180.9 (CO). IR (KBr): v = 3269, 3077, 3055, 3045, 3023, 2917, 2849

(w), 1638 (s), 1622 (m), 1589 (s), 1574 (w), 1548 (m) , 1519, 1514 (w) , 1491 (m), 1462 (w),

1441 (m), 1429 (s), 1358 (w), 1313, 1306 (s), 1286, 1251, 1235 (m), 1177 (w), 1163, 1115,

1076, 1069, 1049 (m), 1033 (w), 1022 (m), 1001, 975, 961 (w), 934 (m), 908, 875, 717, 690, 852

��

(w), 838, 823 (m), 811, 767 (w), 752, 730, 692 (s), 652, 638, 619, 609, 604 (m), 548 (w), 530 (s)

cm−1. GC-MS (EI, 70 eV): m/z (%) = 364 ([M]+, 50), 363 (([M-H]+, 100). HRMS (EI, 70 eV):

calcd for C25H15OS [M-H]+,�� !#�#�%��)�34,�� !#��9

1,4-Bis(4-fluorophenyl)-9H-thioxanthen-9-one (9f): Starting with 8 (100 mg, 0.197 mmol),

4-flourophenylboronic acid 3j (66 mg, 0.47 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 9f was isolated as a

1��)?� 2)��4� �� 0:�� #�@�%� ��/7.�)3� .�06��/.��,� '!"�� )�� #� $ � �6 �# -

188°C. 1H NMR (300 MHz, CDCl3): � = 7.04 (t, 2H, J = 8.76 Hz, ArH),

7.14 (d, 2H, J = 8.70 Hz, ArH), 7.17-7.23 (m, 3H, ArH), 7.27-7.51 (m, 6H,

ArH), 8.18 (dd, 1H, J = 1.05, 8.61 Hz, ArH). 19F NMR (282.4 MHz, CDCl3):

� = -115.9, -112.6. 13C NMR (75.5 MHz, CDCl3): � = 113.9 (d, JF,C = 21.5

Hz, CH), 114.8 (d, JF,C = 21.7 Hz, CH), 124.5, 125.4 (CH), 127.1 (C), 128.2

(CH), 128.4 (d, JF,C = 7.87 Hz, CH), 128.7 (CH), 129.9 (C), 130.4 (d, JF,C = 8.27 Hz, CH),

130.9, 131.0 (CH), 133.3 (d, JF,C = 3.35 Hz, C), 135.0, 136.8, 137.1 (C), 138.3 (d, JF,C = 3.61 Hz,

C), 143.1 (C), 160.7 (d, JF,C = 245.5 Hz, C-F), 161.9 (d, JF,C = 248.6 Hz, C-F), 180.8 (CO). IR

(KBr): v = 3072, 3045, 2961, 2920, 2850 (w), 1639 (s), 1600 (m), 1590 (s), 1558, 1550 (w),

1506 (s), 1463 (w), 1434 (s), 1406, 1359 (w), 1307 (m), 1288, 1279, 1259 (w), 1220 (s), 1168

(w), 1157, 1090 (m), 1070, 1043, 1033 (w), 1013 (m), 961 (w), 931 (m), 866 (w), 845 (m), 823,

797 (s), 785 (m), 760, 738 (s), 688 (w), 660, 650, 641 (m), 630, 608 (w), 591 (m), 553, 533 (s)

cm−1. GC-MS (EI, 70 eV): m/z (%) = 400 ([M]+, 59), 399 ([M-H]+, 100). HRMS (EI, 70 eV):

calcd for C25H31F2OS [M-H]+: �'' ! �'9%��)�34,��'' ! ��

Synthesis of 1-Aryl-4-(trifluorosulfonyloxy)-thioxanthones 10a-i:

�1-(4-Ethylphenyl)-9-oxo-9H-thioxanthen-4-yltrifluoromethanesulfonate (10a): Starting with

8 (100 mg, 0.197 mmol), 4-ethylphenylboronic acid 3b (32 mg, 0.22

mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg, 0.29 mmol) and

THF (5 mL), 10a was isolated as a 1��)?�2)��4�#��0:��'!@�%�reaction

temperature: 65°C for 8 h. Mp.196-198°C (CH2Cl2/EtOH 1:1). 1H

NMR (300 MHz, CDCl3): � = 1.23 (t, 3H, J = 7.6 Hz, CH3), 2.67 (q,

2H, J = 7.6 Hz, CH2), 7.10 (d, 2H, J = 8.20 Hz, ArH), 7.15-7.20 (m,

2H, ArH), 7.25 (d, 1H, J = 8.4 Hz, ArH), 7.27-7.41 (m, 1H, ArH), 7.49-7.54 (m, 3H, ArH), 8.19

(dd, 1H, J = 0.99, 8.10 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -73.1. 13C NMR

�

�

��

��

(75.5 MHz, CDCl3): � = 14.2 (CH3), 27.6 (CH2), 117.6 (q, JF,C = 318.7 Hz, CF3), 122.1, 124.8,

126.1, 126.6, 126.7 (CH), 128.2 (C), 128.6, 129.1 (CH), 130.0 (C), 131.4 (CH), 132.8, 138.1,

142.2, 142.4, 145.0, 179.3 (CO). IR (KBr): v = 3060, 3028, 2960, 2928, 2870, 2852 (w), 1644

(s), 1614 (w), 1593, 1580 (m), 1555, 1511, 1454 (w), 1430 (s), 1372, 1316 (w), 1303 (m), 1274,

1260 (w), 1247 (m), 1219, 1205, 1186 (s), 1160 (m), 1134 (s), 1114, 1079, 1049, 1034, 1017,

971 (m), 883 (s), 857, 836, 831 (m), 802, 756, 739 (s), 724 (m), 693, 666, 652 (w), 640 (s), 632

(m), 603, 590 (s), 566, 535 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 464 ([M]+, 26), 331 (100),

302 (89), 274 (24). HRMS (EI, 70 eV): calcd for C22H15F3O4S2 [M]+,� � � !��#�%� �)�34,�

464.03664.

1-(4-(Tert-butyl)phenyl)-9-oxo-9H-thioxanthen-4-yltrifluoromethanesulfonate(10b):�Starting

with 8 (100 mg, 0.197 mmol), 4-tert-butylphenylboronic acid 3c (39

mg, 0.22 mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg, 0.29

mmol) and THF (5 mL), 10b was isolated as a yellow solid (74 mg,

9 @�%� reaction temperature: 65°C for 8 h. Mp.181-183°C. 1H NMR

(300 MHz, CDCl3): � = 1.32 (s, 9H, 3CH3), 7.13 (d, 2H, J = 8.48 Hz,

ArH), 7.27 (d, 1H, J = 8.48 Hz, ArH), 7.35-7.39 (m, 3H, ArH), 7.52 (d,

1H, J = 8.48 Hz, ArH), 7.55-7.60 (m, 2H, ArH), 8.22 (dd, 1H, J = 0.99, 8.07 Hz, ArH). 19F NMR

(282.4 MHz, CDCl3): � = -73.1. 13C NMR (75.5 MHz, CDCl3): � = 30.4 (3CH3), 33.6 (C), 117.6

(q, JF,C = 320.8 Hz, CF3), 122.1, 123.9, 124.8, 126.1, 126.5 (CH), 128.2 (C), 128.6, 129.3 (CH),

130.1 (C), 131.4 (CH), 132.8, 137.8, 142.4, 145.0, 149.1 (C), 179.4 (CO). IR (KBr): v = 3106,

3071, 3027, 2959, 2903, 2865 (w), 1643 (s), 1614 (w), 1591, 1582 (m), 1507, 1474, 1461 (w),

1419 (s), 1373, 1316 (w), 1305 (m), 1283, 1263, 1247, 1238 (w), 1214 (s), 1187 (m), 1269,

1160 (w), 1130 (s), 1115 (m), 1078, 1052, 1035,1014 (w), 972 (m), 906 (w), 884 (s), 854 (w),

844, 821 (m), 796 (s), 765 (w), 758 (m), 747 (w), 735 (s), 720 (m), 686, 666, 653, 632 (w), 603

(s), 593 (m), 573, 564 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 492 ([M]+, 41), 477 (13), 359

(68), 344 (23), 303 (63), 302 (100), 274 (15). HRMS (EI, 70 eV): calcd for C24H19F3O4S2 [M]+:

�'� ! 9��%��)�34,��'� ! �#

��

9-Oxo-1-(p-tolyl)-9H-thioxanthen-4-yl trifluoromethanesulfonate (10c): Starting with 8 (100

mg, 0.197 mmol), 4-methylphenylboronic acid 3e (30 mg, 0.22 mmol),


mL), 10c was isolated as a 1��)?� 2)��4� 99� 0:�� #9@�%� reaction

temperature: 65°C for 8 h. Mp.130-132°C. 1H NMR (300 MHz, CDCl3):

� = 2.37 (s, 3H, CH3), 7.09 (d, 2H, J = 8.16 Hz, ArH), 7.16-7.19 (m, 2H,

ArH), 7.25 (d, 1H, J = 8.61 Hz, ArH), 7.35-7.42 (m, 1H, ArH), 7.52-7.57

(m, 3H, ArH), 8.22 (d, 1H, J = 8.16 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -73.1. 13C

NMR (75.5 MHz, CDCl3): � = 21.37 (CH3), 118.6 (q, JF,C = 320.7 Hz, CF3), 123.1, 125.9, 127.2,

127.7, 128.9 (CH), 129.2 (C), 129.6, 130.1 (CH), 131.1 (C), 132.4 (CH), 132.5, 133.8, 137.1,

138.9, 143.4, 146.1 (C), 180.4 (CO). IR (KBr): v = 3290, 3090, 3055, 3028, 2953, 2921, 2850,

2666 (w), 1652 (s), 1614 (w), 1589, 1582 (m), 1552, 1515, 1463 (w), 1436 (m), 1424 (s), 1407

(m), 1312 (w), 1301, 1294, 1248 (m), 1206, 1190 (s), 1166 (w), 1157 (m), 1137, 1131 (s), 1109

(m), 1076, 1050, 1034, 1017 (w), 968 (m), 945, 934 (w), 883 (s), 872 (m), 851 (w), 834, 801 (s),

780 (m), 760, 732 (s), 689, 675, 649, 639 (w), 618, 601, 590 (s), 571 (m), 563, 552 (w), 533 (m)

cm−1. GC-MS (EI, 70 eV): m/z (%) = 450 ([M]+, 43), 317 (100), 302 (78), 274 (17). HRMS (EI,

70 eV): calcd for C21H13F3O4S2 [M]+,��! !�!�'%��)�34,��! !�' 9

1-(4-Chlorophenyl)-9-oxo-9H-thioxanthen-4-yl trifluoromethanesulfonate (10d): Starting

with 8 (100 mg, 0.197 mmol), 4-chlorophenylboronic acid 3f (34 mg,

0.22 mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg, 0.29 mmol)

and THF (5 mL), 10d was isolated as a 1��)?� 2)��4� 9#�0:��#�@�%�


(300 MHz, CDCl3): � = 7.12 (d, 2H, J = 8.45 Hz, ArH), 7.22 (d, 1H, J

= 8.45 Hz, ArH), 7.33 (d, 2H, J = 8.45 Hz, ArH), 7.38-7.43 (m, 1H,

ArH), 7.54-7.61 (m, 3H, ArH), 8.22 (d, 1H, J = 8.12 Hz, ArH). 19F NMR (282.4 MHz, CDCl3):

� = -73.1. 13C NMR (75.5 MHz, CDCl3): � = 118.6 (q, JF,C = 320.8 Hz, CF3), 123.3, 126.0,

127.3, 128.4, 129.1, 129.7, 129.9 (CH), 130.7, 131.2 (C), 132.7 (CH), 132.9, 133.4, 133.8, 140.4,

143.8, 144.7 (C), 180.1 (CO). IR (KBr): v = 3281, 3097, 3066, 2922, 2853, 2667, 2554 (w), 1649

(s), 1614 (w), 1588 (m), 1568, 1551, 1492, 1464, 1455 (w), 1424 (s), 1407, 1397 (m), 1377,

1315 (w), 1302, 1294 (m), 1277, 1247, 1238 (w), 1223, 1205, 1209, 1188 (s), 1158 (m), 1135,

1129 (s), 1090, 1077 (m), 1048, 1035 (w), 1012, 971 (m), 881 (s), 871 (m), 847, 834 (m), 815,

805, 759 (s), 739 (w), 734 (s), 711, 686, 665 (w), 647, 631 (m), 615, 601 (s), 588 (m), 568, 555,

��

538 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 470 ([M+H]+, 38), 337 (100), 302 (68), 274 (26),

245 (14). HRMS (EI, 70 eV): calcd for C20H10F3ClO4S2 [M]+: 469.' �� %��)�34,�� ' ' �9�

1-(4-Methoxyphenyl)-9-oxo-9H-thioxanthen-4-yl trifluoromethanesulfonate (10e): Starting

with 8 (100 mg, 0.197 mmol), 4-methoxyphenylboronic acid 3h (33 mg,


and THF (5 mL), 10e was isolated as a 1��)?� 2)��4� 9�� 0:�� #�@�%�

reaction temperature: 65°C for 8 h. Mp.162-164°C. 1H NMR (300 MHz,

CDCl3): � = 3.79 (s, 3H, OCH3), 6.89 (d, 2H, J = 8.31 Hz, ArH), 7.12

(d, 2H, J = 8.31 Hz, ArH), 7.25 (d, 1H, J = 8.31 Hz, ArH ), 7.35-7.41

(m, 1H, ArH), 7.50-7.56 (m, 3H, ArH), 8.21 (d, 1H, 8.31 Hz, ArH). 19F NMR (282.4 MHz,

CDCl3): � = -73.1. 13C NMR (75.5 MHz, CDCl3): �= 54.2 (OCH3), 112.6 (CH),117.6 (q, JF,C =

320.9 Hz, CF3), 122.1, 124.8, 126.1, 128.0 (CH), 128.1 (C), 128.6, 129.1 (CH), 130.1 (C), 131.4

(CH), 131.5, 132.8, 133.0, 142.3, 144.7, 158.0 (C), 179.5 (CO). IR (KBr): v = 3290, 3104, 3071,

3034, 2996, 2950, 2934, 2907, 2853, 2833, 1682 (w), 1652 (s), 1607 (w), 1589, 1589 (m), 1567,

1552 (w), 1513 (m), 1464, 1455 (w), 1424 (s), 1375, 1353, 1314 (w), 1303, 1295 (m), 1271 (w),

1248, 1241 (m), 1224, 1202, 1191, 1178 (s), 1164, 1157 (w), 1131 (s), 1108 (m), 1078, 1055,

1035 (w), 1026, 972 (m), 885 (s), 846 (m), 832 (w), 819, 807 (s), 779 (w), 761, 734 (s), 690, 673

(w), 650, 643 (m), 619, 599, 592 (s), 574, 544 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 466

([M]+, 36), 333 (100), 302 (31), 274 (10). HRMS (EI, 70 eV): calcd for C21H13F3O5S2 [M]+:

� !��!%��)�34,�� !��'

9-Oxo-1-phenyl-9H-thioxanthen-4-yl trifluoromethanesulfonate (10f): Starting with 8 (100

mg, 0.197 mmol), phenylboronic acid 3i (27 mg, 0.22 mmol),


mL), 10f was isolated as a 1��)?� 2)��4� 9 � 0:�� ##@�%� reaction


CDCl3): � = 7.17-7.21 (m, 1H, ArH), 7.26 (d, 2H, J = 8.37 Hz, ArH),

7.35-7.42 (m, 4H, ArH), 7.53-7.57 (m, 3H, ArH), 8.21 (dd, 1H, J = 0.90, 8.01 Hz, ArH). 19F

NMR (282.4 MHz, CDCl3): � = -73.1. 13C NMR (75.5 MHz, CDCl3): � = 117.6 (q, JF,C = 318.8

Hz, CF3), 122.1, 124.9, 126.2, 126.3, 126.7, 127.1 (CH), 128.2 (C), 128.6, 129.0 (CH), 129.9

(C), 131.5 (CH), 131.6, 132.8, 140.9, 142.5, 145.0 (C), 179.2 (CO). IR (KBr): v = 3274, 3064,

2960, 1901 (w), 1667 (w), 1645 (s), 1622 (w), 1587 (m), 1552, 1493, 1461 (m), 1427 (s), 1409

��

(m), 1315, 1305 (w), 1292 (m), 1260, 1251 (w), 1227, 1207, 1187 (s), 1158 (m), 1129 (s), 1112,

1079, 1054, 1034, 1020, 971 (m), 912 (w), 879 (s), 861 (w), 842 (s), 821 (w), 799 (s), 768 (m),

756 (s), 738, 732, 701, 695, 680 (m), 651 (w), 637 (m), 616 (w), 598 (s), 569, 554 (w), 535 (m)

cm−1. GC-MS (EI, 70 eV): m/z (%) = 436 ([M]+, 36), 303 (100), 302 (45), 274 (38), 245 (12).

HRMS (EI, 70 eV): calcd for C20H11F3O4S2 [M]+,�� !!��%��)�34,�� !!�!

1-(4-Fluorophenyl)-9-oxo-9H-thioxanthen-4-yl trifluoromethanesulfonate (10g): Starting

with 8 (100 mg, 0.197 mmol), 4-flourophenylboronic acid 3j (31 mg,


and THF (5 mL), 10g was isolated as a 1��)?� 2)��4� 9�� 0:�� #�@�%�

reaction temperature: 65°C for 8 h. Mp.157-159°C. 1H NMR (300 MHz,

CDCl3): � = 7.05 (t, 2H, J = 8.73 Hz, ArH), 7.12-7.18 (m, 2H, ArH),

7.23 (d, 1H, J = 8.21 Hz, ArH), 7.37-7.43 (m, 1H, ArH), 7.53-7.61 (m,

3H, ArH), 8.21 (d, 1H, J = 8.10 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -114.9, -73.1. 13C

NMR (75.5 MHz, CDCl3): � = 114.1 (d, JF,C = 21.6 Hz, CH), 117.6 (q, JF,C = 320.9 Hz, CF3),

122.2, 124.9, 126.3 (CH), 128.1(C), 128.4(d, JF,C = 7.98 Hz, CH), 128.6, 129.0 (CH), 129.7 (C),

131.6 (CH), 131.8, 132.8 (C), 136.7 (d, JF,C = 3.45 Hz, C), 142.7, 143.9 (C), 161.2 (d, JF,C =

245.4 Hz, C-F), 179.1 (CO). IR (KBr): v = 3068, 3044, 2957, 2917, 2848 (w), 1649 (s), 1620,

1601 (w), 1589 (m), 1567, 1551 (w), 1510 (m), 1463 (w), 1429 (s), 1408 (m), 1370, 1316, 1303,

1293, 1248 (w), 1213 (s), 1188, 1156 (m), 1129 (s), 1092, 1078, 1048, 1034, 1012 (w), 972 (m),

883 (s), 871, 843 (m), 832 (s), 815 (m), 804 (s), 791 (m), 761 (s), 741 (w), 733 (m), 690, 674

(w), 650, 639 (m), 617, 598 (s), 588, 571 (m), 563, 549 (w), 537 (m) cm−1. GC-MS (EI, 70 eV):

m/z (%) = 454 ([M+H]+, 33), 321 (100), 292 (42), 263 (13). HRMS (EI, 70 eV): calcd for

C20H10F4O4S2 [M]+,�� ''��%��)�34,�� ''��!

9-Oxo-1-(o-tolyl)-9H-thioxanthen-4-yl trifluoromethanesulfonate (10h): Starting with 8 (100

mg, 0.197 mmol), 2-methylphenylboronic acid 3l (30 mg, 0.22 mmol),


mL), 10h was isolated as a 1��)?� 2)��4� 9� 0:�� 9 @�%� reaction


� = 1.95 (s, 3H, CH3), 6.97 (d, 1H, J = 7.23 Hz, ArH), 7.17 (d, 1H, J =

3.51 Hz, ArH), 7.19-7.29 (m, 3H, ArH), 7.33-7.39 (m, 1H, ArH), 7.54-7.58 (m, 3H, ArH), 8.22

(dd, 1H, J = 8.11 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -73.1. 13C NMR (75.5 MHz,

��

CDCl3): � = 20.2 (CH3), 118.6 (q, JF,C = 320.9 Hz, CF3), 123.4, 125.6, 126.0, 127.2, 127.3, 127.4

(CH), 129.4 (C), 129.5, 129.6, 129.8 (CH), 130.3, 132.4 (C), 132.6 (CH), 133.9, 134.6, 141.9,

143.6, 145.5 (C), 179.6 (CO). IR (KBr): v = 3292, 3063, 3018, 2953, 2922, 2857 (w), 1650 (s),

1592 (m), 1554, 1489 (w), 1425 (s), 1377 (w), 1301 (m), 1271 (w), 1261 (w), 1248 (m), 1209,

1188 (s), 1161 (m), 1133, 1118 (s), 1078, 1055, 1035 (w), 974 (m), 884 (s), 838 (m), 800 (s), 785

(w), 752, 737, 729 (s), 693, 675 (w), 650 (m), 602 (s), 568, 536 (w) cm−1. GC-MS (EI, 70 eV):

m/z (%) = 450 ([M]+, 30), 435 (16), 317 (68), 302 (100), 274 (30). HRMS (EI, 70 eV): calcd for

C21H13F3O4S2 [M]+,��! !�!�'%��)�34,��! !�!�'

9-Oxo-1-(m-tolyl)-9H-thioxanthen-4-yl trifluoromethanesulfonate (10i): Starting with 8 (100

mg, 0.197 mmol), 3-methylphenylboronic acid 3m (30 mg, 0.22

mmol), Pd(PPh3)4 (11 mg, 5 mol%), K3PO4 (63 mg, 0.29 mmol) and

THF (5 mL), 10i was isolated as a 1��)?�2)��4�9!�0:��9'@�%�reaction


CDCl3): � = 2.37 (s, 3H, CH3), 6.98 (d, 1H, J = 7.52 Hz, ArH), 7.02

(brs, 1H, ArH), 7.15 (d, 1H, J = 7.52 Hz, ArH), 7.22-7.27 (m, 2H, ArH), 7.36-7.42 (m, 1H,

ArH), 7.51-7.57 (m, 3H, ArH), 8.22 (d, 1H, J = 8.14 Hz, ArH). 19F NMR (282.4 MHz, CDCl3):

� = -73.1. 13C NMR (75.5 MHz, CDCl3): � = 20.5 (CH3), 117.6 (q, JF,C = 320.7 Hz, CF3), 122.1,

123.9, 124.9, 126.2, 126.9, 127.1, 127.4 (CH), 128.2 (C), 128.6, 129.0 (CH), 130.0 (C), 131.5

(CH), 132.8, 136.7, 140.8, 142.5, 145.1 (C), 179.2 (CO). IR (KBr): v = 3283, 3061, 2961, 2922,

2859, 2736, 2668, 2554 (w), 1651 (s), 1613, 1605 (w), 1589 (m), 1568, 1552, 1537, 1484, 1463

(w), 1426 (s), 1387, 1314 (w), 1300, 1292 (m), 1261 (w), 1249 (m), 1230, 1202 (s), 1183, 1167,

1158 (m), 1131 (s), 1119 (m), 1094, 1078, 1035 (w), 970 (m), 900 (w), 880 (s), 864 (w), 840,

806, 792, 774 (s), 763 (w), 751 (s), 740 (w), 727, 702 (m), 692, 679, 653 (w), 634 (m), 600 (s),

568, 551 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) = 450 ([M]+, 33), 317 (100), 302 (37), 288 (12).

HRMS (EI, 70 eV): calcd for C21H13F3O4S2 [M]+,��! !�!�'%��)�34,��! !�''#

General procedure for the synthesis of unsymmetrical diarylthioxanthones 11a-d:�

The reaction was carried out in a pressure tube. To a THF suspension (4-5 mL) of 1,4-

bis(triflates) 8 (100 mg, 0.197 mmol), Pd(PPh3)4 (5 mol%) and of the Ar1B(OH)2 (1.1 equiv.),

K3PO4 (1.5 equiv.) was added. The mixture was heated at the indicated temperature at (65°C)

under Argon atmosphere for the indicated period of time (8 h) and cooled to room temperature,

then Ar2B(OH)2 (1.1 equiv.) was added, the reaction mixture was further heated at (90°C) for (6

��

h). The reaction mixture was again cooled to room temperature and diluted with water and

extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were dried (Na2SO4), filtered

and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography

(silica gel, EtOAc/ heptanes).

1-(4-Methoxyphenyl)-4-(p-tolyl)-9H-thioxanthen-9-one (11a): Starting with 8 (100 mg,

0.197mmol), 4-methoxyphenylboronic acid 3h (33 mg, 0.22 mmol), 4-

methylphenylboronic acid 3e (29 mg, 0.22 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 11a was isolated as a

1��)?�2)��4�9��0:��'!@�%�reaction temperature: at 65°C for 8 h, at 90°C for

6 h. Mp.160-162°C. 1H NMR (300 MHz, CDCl3): � = 2.39 (s, 3H, CH3),

3.79 (s, 3H, OCH3), 6.89 (d, 2H, J = 8.76 Hz, ArH), 7.16-7.22 (m, 2H, ArH),

7.24-7.45 (m, 9H, ArH), 8.18 (dd, 1H, J = 1.08, 8.04 Hz, ArH).13C NMR

(75.5 MHz, CDCl3): � = 21.44 (CH3), 55.2 (OCH3), 113.5, 125.5, 126.2

(CH), 128.1 (C), 129.1, 129.2, 129.4, 129.6, 129.8 (CH), 131.4 (C), 131.7, 132.0 (CH), 135.7,

135.8, 136.4, 137.5, 138.5, 138.6, 144.5, 158.6 (C), 182.4 (CO). IR (KBr): v = 3055, 3029, 3008,

2955, 2918, 2857, 2835 (w), 1635 (s), 1606, 1591 (m), 1576, 1548 (w), 1512 (m), 1461 (w),

1434 (s), 1410, 1384, 1359 (w), 1318, 1307, 1290 (m), 1271 (w), 1254 (m), 1241 (s), 1172 (m),

1161, 1118, 1105, 1080, 1073 (w), 1149,1026, 1019 (m), 973, 964, 935 (w), 920 (m), 902, 865,

854, 834 (w), 825 (m), 813 (s), 772 (w), 758, 731, 719 (s), 687, 660 (w), 651, 644 (m), 634, 609,

593 (w), 563 (m), 547 (w), 537 (s) cm−1. GC-MS (EI, 70 eV): m/z (%) = 409 ([M+H]+, 23), 408

([M]+, 76), 407 ([M-H]+, 100). HRMS (ESI): calcd for C27H21O2S [M+H]+,��!' �� #%� �)�34,�

409.12630.

1-(4-Fluorophenyl)-4-(4-methoxyphenyl)-9H-thioxanthen-9-one (11b): Starting with 8 (100

mg, 0.197 mmol), 4-flourophenylboronic acid 3j (30 mg, 0.22 mmol), 4-

methoxyphenylboronic acid 3h (33 mg, 0.22 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 11b was isolated as a

1��)?�2)��4� 9��0:��##@�%�reaction temperature: at 65°C for 8 h, at 90°C

for 6 h. Mp.194-196°C. 1H NMR (300 MHz, CDCl3): � = 3.80 (s, 3H,

OCH3), 7.05 (q, 4H, J = 8.76 Hz, ArH), 7.19-7.24 (m, 3H, ArH), 7.28-7.48

(m, 6H, ArH), 8.19 (dd, 1H, J = 1.05, 8.01 Hz, ArH). 19F NMR (282.4 MHz,

CDCl3): � = -116.2. 13C NMR (75.5 MHz, CDCl3): � = 54.3 (OCH3), 113.1

��

(CH), 113.9 (d, JF,C = 21.5 Hz, CH), 124.5, 125.2 (CH), 127.0 (C), 128.2 (CH), 128.4 (d, JF,C =

7.99 Hz, CH), 128.7 (CH), 129.6 (C), 129.8 (CH), 129.9 (C), 130.8, 131.1 (CH) 135.4, 137.1,

137.9 (C), 138.5 (d, JF,C = 3.42 Hz, C), 142.7, 158.9 (C), 160.8 (d, JF,C = 245.4 Hz, C-F), 180.9

(CO). IR (KBr): v = 3057, 3031, 2954, 2920, 2850, 2251 (w), 1633 (s), 1601 (m), 1589 (s), 1574,

1548 (w), 1509 (s), 1461 (m), 1434 (s), 1359 (w), 1305, 1307, 1290 (m), 1245, 1219 (s), 1174,

1157 (m), 1105, 1092, 1081, 1045 (w), 1022 (s), 965, 931, 914, 896, 877, 867 (w), 844 (m), 828,

821 (s), 795 (m), 777 (w), 760, 731, 725 (s), 700, 689 (w), 662, 649, 641 (m), 628 (w), 607, 593

(m), 561, 550 (m), 535 (s) cm−1. GC-MS (EI, 70 eV): m/z (%) = 412 ([M]+, 78), 411 ([M-H]+,

100), 368 (14). HRMS (EI, 70 eV): calcd for C26H16FO2S [M-H]+,�� !#�' %��)�34,�� !#�'��

4-(4-(Tert-butyl)phenyl)-1-(4-methoxyphenyl)-9H-thioxanthen-9-one (11c): Starting with 8

(100 mg, 0.197 mmol), 4-methoxyphenylboronic acid 3h (33 mg, 0.22 mmol),

4-tert-butylphenylboronic acid 3c (39 mg, 0.22 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 11c was isolated as a

1��)?�2)��4�9��0:��#�@�%�reaction temperature: at 65°C for 8 h, at 90°C for

6 h. Mp.212-214°C. 1H NMR (300 MHz, CDCl3): � = 1.35 (s, 9H, 3CH3),

3.80 (s, 3H, OCH3), 6.89 (d, 2H, J = 8.64 Hz, ArH), 7.18 (d, 2H, J = 8.70 Hz,

ArH), 7.22-7.43 (m, 7H, ArH),7.47 (d, 2H, J = 8.31 Hz, ArH), 8.18 (dd, 1H, J

= 0.90, 7.89 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 30.4 (CH3), 33.8

(C), 54.2 (OCH3), 112.5, 124.5, 124.6, 125.1 (CH), 127.0 (C), 128.1, 128.3, 128.8, 129.8 (CH),

130.3 (C), 130.6, 131.0 (CH), 134.5, 134.8, 135.4, 136.5, 137.6, 143.4, 150.5, 157.5 (C), 181.4

(CO). IR (KBr): v = 3059, 2997, 2959, 2931, 2903, 2866, 2834, 2248 (w), 1640, 1633 (s), 1606,

1589 (m), 1575, 1558, 1544 (w), 1510 (s), 1461 (m), 1350 (w), 1433 (s), 1410, 1360 (w), 1306

(m), 1290, 1271 (w), 1240 (s), 1174 (m), 1139 (w), 1113, 1105 (m), 1081 (w), 1049 (m), 1026,

1015 (m), 972, 935, 918, 907, 888, 863, 847, 838 (w), 817 (s), 779 (w), 759 (m), 744 (w), 729

(s), 688 (w), 649 (m), 630, 621, 607, 594 (w), 568, 545 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) =

451 ([M+H]+, 28), 450 ([M]+, 91), 449 ([M-H]+, 100), 435 (12). HRMS (EI, 70 eV): calcd for

C30H25O2S [M-H]+: 449.�� '#%��)�34,��' �� !

�

�

��

��

4-(3-Chlorophenyl)-1-(4-methoxyphenyl)-9H-thioxanthen-9-one (11d): Starting with 8 (100

mg, 0.197 mmol), 4-methoxyphenylboronic acid 3h (33 mg, 0.22 mmol),

3-chlorophenylboronic acid 3n (34 mg, 0.22 mmol), Pd(PPh3)4 (23 mg, 10

mol%), K3PO4 (125 mg, 0.59 mmol) and THF (5 mL), 11d was isolated as

a 1��)?�2)��4�9��0:��#'@�%�reaction temperature: at 65°C for 8 h, at 90°C

for 6 h. Mp.190-191°C. 1H NMR (300 MHz, CDCl3): � = 3.79 (s, 3H,

OCH3), 6.88 (d, 2H, J = 8.73 Hz, ArH), 7.17 (d, 2H, J = 8.73 Hz, ArH),

7.24 (d, 1H, J = 7.62 Hz, ArH), 7.28-7.46 (m, 8H, ArH), 8.18 (dd, 1H, J =

1.08, 8.04 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): � = 55.2 (OCH3), 113.6, 125.5, 126.4, 128.0

(CH), 128.2 (C), 128.7, 129.2, 129.3, 129.8, 129.9, 130.0 (CH), 131.3 (C), 131.9 (CH), 134.6,

135.5, 135.9, 137.1, 137.3, 140.3, 145.2, 158.7 (C), 182.2 (CO). IR (KBr): v = 3100, 3070, 3053,

2998, 2947, 2931, 2902, 2831 (w), 1650 (s), 1633 (s), 1605 (w), 1588 (m), 1575, 1564, 1546 (w),

1510 (m), 1462, 1454 (w), 1432 (s), 1407, 1365 (w), 1307, 1299 (m), 1288 (w), 1237 (s), 1178

(m), 1165, 1155, 1121 (w), 1106, 1074, 1049, 1025 (m), 963 (w), 941 (m), 928, 898, 885, 866

(w), 841 (m), 819 (s), 783, 779 (m), 762 (s), 748 (w), 734 (s), 715, 692 (m), 665, 645, 623, 609,

583, 571 (w), 546 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) = 428 ([M]+, 72), 427 ([M-H]+, 100),

413 (10). HRMS (EI, 70 eV): calcd for C26H16ClO2S [M-H]+,��9 !��!%��)�34,��9 !��

Site-Selective Synthesis of Arylated Indenones by Suzuki–Miyaura Cross-Coupling

Reactions of 2,3,5-Tribromoinden-1-one

Synthesis of 2,3,5-Tribromo-1H-inden-1-one (13): A round bottom flask was equipped with

condenser. Benzene suspension (35 mL) of 5-bromo-indanone 12 (1.50 g,

7.10 mmol), N-bromosccinamide (4.43 g, 24.9 mmol) and AIBN (0.12 g,

10 mol %) was refluxed under Argon for 7 h and then cooled to 20°C.

Reaction mixture was quenched with triethylamine (1 mL) and benzene

was evaporated in vacuo. Then reaction mixture was diluted with water and extracted with

CH2Cl2 (3 x 25 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate

was concentrated in vacuo. The residue was purified by flash chromatography (silica gel,

heptanes). 14 were isolated as light yellow crystalline solid (1.60 g, 62%).Mp.160-161°C. 1H

NMR (300 MHz, CDCl3): δ = 7.26 (d, 1H, J = 7.65 Hz, ArH), 7.28 (d, 1H, J = 1.50 Hz, ArH),

7.41 (dd, 1H, J = 1.62, 7.65 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 123.8 (C), 124.0,

124.7 (CH), 127.6, 129.4 (C), 132.6 (CH), 144.1, 144.6 (C), 185.4 (CO). IR (KBr): v = 3416,

� ��

3084, 3015, 2922, 2850, 2674 (w), 1722 (s), 1594, 1584 (w), 1540, 1438, 1401, 1337 (m), 1260,

1218 (w), 1200 (s), 1094 (m), 1085, 1054 (s), 1041(m), 959 (w), 933, 876 (s), 811(m), 764, 691,

680 (s), 618, 593, 577 (m). GC-MS (EI, 70 eV): m/z (%) = 370 ([(M+H), 81Br, 81Br, 81Br]+, 13),

368 ([(M+H), 79Br, 81Br, 81Br]+, 41), 366 ([(M+H), 79Br, 79Br, 81Br]+, 42), 364 ([(M+H), 79Br, 79Br, 79Br]+, 15), 287 (100), 259 (23), 178 (17). HRMS (EI, 70 eV): calcd for C9H3Br3O [M, 81Br, 81Br, 81Br]+,�� ' 9 9�%��)�34,�� ' 9 �''��7/�74��)��9H3Br3O [M, 79Br, 81Br, 81Br]+,�� 9 9 #9 %�

found: 367.76801, calcd for C9H3Br3O [M, 79Br, 79Br, 81Br]+,� � � 99!#�%� �)�34,� � � 99!!��

calcd for C9H3Br3O [M, 79Br, 79Br, 79Br]+,�� 99�#�%��)�34,�� 99�#�

General procedure (A) for Suzuki cross-coupling reactions of brominated indenone (13): The

reaction was carried out in a pressure tube. To a 1,4-dioxane suspension (3-5 mL) of the

brominated indenone, Pd(PPh3)4 or Pd(PPh3)2Cl2 (3-5 mol%) and of the arylboronic acid (1.0-1.1

per cross coupling), K3PO4 (1.5 equiv. per cross coupling) or an aqueous solution of K2CO3 (2

M, 1 mL) was added. The mixture was heated at the indicated temperature (45-70°C) under

Argon atmosphere for the indicated period of time (6-9 h). The reaction mixture was diluted with

water and extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were dried

(Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by flash

chromatography (silica gel, EtOAc/ heptanes).

Synthesis of triaryl-1H-inden-1-ones 14a-g:

2,3,5-Triphenyl-1H-inden-1-one (14a): Starting with 13 (80 mg, 0.22 mmol), Pd(PPh3)4 (13

mg, 5 mol%), 1,4-dioxane (5 mL), K2CO3 (2 M, 1 mL) and

phenylboronic acid 3i (88 mg, 0.72 mmol), 16a was isolated as a

brownish yellow solid (65 mg, 83%). reaction temperature: 70°C

for 6 h. Mp.182-183°C. 1H NMR (300 MHz, CDCl3): δ = 7.17-

7.21 (m, 5H, ArH), 7.26-7.42 (m, 10H, ArH), 7.46-7.49 (m, 2H,

ArH), 7.57 (d, 1H, J = 7.44 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 120.5, 123.4, 127.2,

127.5, 127.8, 128.1, 128.3, 128.5, 128.9, 129.3 (CH), 129.5 (C), 130.0 (CH), 130.7, 132.7, 133.2,

140.4, 146.1, 146.8, 154.8 (C), 196.1 (CO). IR (KBr): v = 3388, 3054, 3030, 2955, 2921, 2849

(w), 1704, 1597 (s), 1573, 1485, 1467, 1442 (w), 1355 (m), 1340, 1331, 1279, 1263, 1184 (w),

1177 (m), 1160, 1143 (w), 1097, 1079, 1063, 1029 (m), 1012, 1000, 963 (w), 939 (m), 917 (w),

894, 850, 837, 793, 778 (m), 758 (s), 742 (w), 727, 690 (s), 672, 657, 638 (m), 616 (w), 596 (m),

��

577, 563 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 358 ([M]+, 100), 357 (40), 341 (11). 326 (11),

252 (15). HRMS (EI, 70 eV): calcd for C27H18O [M]+,��# ��%��)�34,��# ��9

2,3,5-Tris (4-ethylphenyl)-1H-inden-1-one (14b): Starting with 13 (80 mg, 0.22 mmol),

Pd(PPh3)4 (13 mg, 5 mol%), 1,4-dioxane (5 mL), K2CO3 (2 M, 1

mL) and 4-ethylphenylboronic acid 3b (108 mg, 0.72 mmol),

14b was isolated as a brownish yellow solid (85 mg, 88%).


(300 MHz, CDCl3): δ =1.16-1.23 (m, 9H, 3CH3), 2.54 (q, 2H, J

= 7.5 Hz, CH2), 2.56-2.66 (m, 4H, 2CH2), 7.02 (d, 2H, J = 8.22

Hz, ArH), 7.13-7.27 (m, 9H, ArH), 7.36 (dd, 1H, J = 1.35, 7.47 Hz, ArH), 7.40 (d, 2H, J = 8.16

Hz, ArH), 7.52 (d, 1H, J = 7.44 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 14.1, 14.2, 14.5

(CH3), 27.5, 27.6, 27.8 (CH2), 119.3, 122.2, 126.0, 126.1, 126.6 (CH), 127.2 (C), 127.2, 127.3,

127.6 (CH), 128.4 (C), 128.9 (CH), 129.1, 131.7, 136.8, 142.7, 143.5, 144.5, 145.3, 145.6, 153.2

(C), 195.4 (CO). IR (KBr): v = 3380, 3023, 2962, 2928, 2873 (w), 1698 (s), 1651, 1633 (w),

1595 (s), 1538, 1516, 1500 (w), 1455 (m), 1410, 1376 (w), 1351 (m), 1336, 1259 (w), 1181 (m),

1142, 1116 (w), 1095, 1071, 1048, 1017, 1012 (m), 965 (w), 936 (m), 895, 865, 851 (w), 821,

786 (s), 740, 729, 703, 674, 660, 638, 623 (w), 568 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 442

([M]+, 100), 413 (26), 207 (26). HRMS (EI, 70 eV): calcd for C33H30O [M]+,�� '��%��)�34,�

442.22947.

2,3,5-Tris (4-tert-butylphenyl)-1H-inden-1-one (14c): Starting with 13 (80 mg, 0.22 mmol),

Pd(PPh3)4 (13 mg, 5 mol%), 1,4-dioxane (5 mL), K2CO3

(2 M, 1 mL) and 4-tert-butylphenylboronic acid 3c (129

mg, 0.72 mmol), 14c was isolated as a brownish yellow

solid (98 mg, 85%). reaction temperature: 70°C for 6 h.

Mp.98-100°C. 1H NMR (300 MHz, CDCl3): δ = 1.23 (s,

9H, 3CH3), 1.27 (s, 9H, 3CH3), 1.29 (s, 9H, 3CH3), 7.16-

7.23 (m, 4H, ArH), 7.28-7.46 (m, 10H, ArH), 7.53 (d, 1H, J = 7.41 Hz, ArH). 13C NMR (75.5

MHz, CDCl3): δ = 31.2 (6CH3), 31.3 (3CH3), 34.6, 34.7, 34.9 (C), 120.5, 123.2, 125.0, 125.7,

125.8, 126.9, 127.0 (CH), 128.0 (C), 128.3 (CH), 129.5 (C), 129.6 (CH), 129.9, 132.6, 146.4,

146.5, 150.6, 151.4, 152.4, 154.2 (C), 196.6 (CO). IR (KBr): v = 3086, 3035, 2958, 2927, 2903,

2866, 2183, 2161, 1737 (w), 1704 (s), 1637, 1667, 1658, 1651, 1642, 1620 (w), 1598 (m), 1536,

�

��

1547, 1526, 1519, 1512, 1495 (w), 1462 (m), 1446, 1423, 1402, 1392 (w), 1362, 1351, 1268,

1187, 1112, 1093, 1069, 1015, 938 (m), 821 (s), 785 (m), 766, 756, 726, 708, 693, 648, 637, 613,

595 (w), 579 (m), 558 (s), 538, 528 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 526 ([M]+, 100),

511 (60). 248 (27). HRMS (EI, 70 eV): calcd for C39H42O [M]+: 526.��!�%��)�34,�� '�

2,3,5-Tris-(3-methoxyphenyl)-1H-inden-1-one (14d): Starting with 13 (80 mg, 0.22 mmol),

Pd(PPh3)4 (13 mg, 5 mol%), 1,4-dioxane (5 mL), K2CO3

(2 M, 1 mL) and 3-methoxyphenylboronic acid 3o (109

mg, 0.72 mmol), 14d was isolated as a brownish yellow

solid (75 mg, 76%). reaction temperature: 70°C for 6 h.

Mp.163-165°C. 1H NMR (300 MHz, CDCl3): δ = 3.60

(s, 3H, OCH3), 3.65 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 6.71-6.90 (m, 6H, ArH), 6.93 (dt, 1H, J

= 1.08, 7.56 Hz, ArH), 7.00 (t, 1H, J = 1.80 Hz, ArH), 7.05-7.14 (m, 2H, ArH), 7.25-7.31 (m,

3H, ArH), 7.40 (dd, 1H, J = 1.44, 7.41 Hz, ArH), 7.56 (d, 1H, J = 7.47 Hz, ArH). 13C NMR (75.5

MHz, CDCl3): δ = 54.5, 54.7, 54.8 (OCH3), 112.6, 112.7, 113.1, 113.6, 114.3, 114.6, 119.1,

120.0, 120.2, 121.9, 122.7, 127.0, 128.5 (CH), 129.0 (C), 129.3, 129.5 (CH), 131.4, 132.5, 133.4,

141.3, 145.4, 146.1, 154.3, 158.5, 159.2, 159.4 (C), 195.3 (CO). IR (KBr): v = 3371, 3070,

2999, 2921, 2852, 2830 (w), 1698, 1599, 1581 (s), 1461, 1465, 1453, 1440, 1432, 1317, 1351,

1329, 1319, 1301 (m), 1290, 1281, 1262, 1236, 1218, 1182, 1165 (s), 1136, 1101, 1079, 1056

(m), 1046, 1032 (s), 992, (w), 962 (m), 923, 907 (w), 879 (m), 845 (s), 795 (m), 784, 767 (s), 739

(w), 729, 699, 685, 675 (s), 641, 621, 603, 590, 554 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) =

448 ([M]+, 100), 417 (11). HRMS (EI, 70 eV): calcd for C30H24O4 [M]+,� ��# � '�%� �)�34,�

448.16680.

2,3,5-Tris (3-chlorophenyl)-1H-inden-1-one (14e): Starting with 13 (80 mg, 0.22 mmol),


mL) and 3-chlorophenylboronic acid 3n (113 mg, 0.72 mmol),

14e was isolated as a brownish yellow solid (80 mg, 79%).

reaction temperature: 70°C for 6 h. Mp.135-137°C. 1H NMR (300

MHz, CDCl3): δ = 7.01 (dt, 1H, J = 1.31, 7.27 Hz, ArH), 7.09-


MHz, CDCl3): δ = 120.3, 123.8, 125.4, 126.6, 127.3, 128.0, 128.1, 128.2, 128.3, 128.4, 129.5

(CH), 129.5 (C), 129.8, 129.9, 130.2, 130.6 (CH), 131.9, 132.5, 134.0, 134.2, 134.9, 135.2,

��

141.9, 145.5, 145.6, 154.0 (C), 194.9 (CO). IR (KBr): v = 3384, 2058, 2955, 2921, 2851 (w),

1699 (s), 1596, 1579, 1561 (m), 1488 (w), 1461(m), 1437, 1423 (w), 1402, 1344, 1328 (m),

1297, 1259, 1249, 1218 (w), 1186 (m), 1163,1149 (w), 1078, 1063 (m), 996, 979 (w), 957 (m),

914, 905 (w), 892, 875, 851, 799 (m), 779, 769, 743, 713 (s), 689 (m), 682, 667 (s), 650, 637,

602, 592, 574, 556, 545 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 464 ([M, 37Cl, 37Cl, 35Cl]+, 37),

462 ([M, 37Cl,35Cl, 35Cl,]+, 98), 460 ([M, 35Cl,

35Cl,�35Cl,]+, 100), 425 (42), 362 (21), 326 (31).

HRMS (EI, 70 eV): calcd for C27H15Cl3O [M, 35Cl, 35Cl,

35Cl,]+,�� ! !�#�!%��)�34,�� ! !�9�!

2,3,5-Tris (4-fluorophenyl)-1H-inden-1-one (14f): Starting with 13 (80 mg, 0.22 mmol),


mL) and 4-fluorophenylboronic acid 3j (101 mg, 0.72 mmol), 14f

was isolated as a brownish yellow solid (73 mg, 81%). reaction


CDCl3): δ = 6.90 (t, 2H, J = 8.79 Hz, ArH), 7.03-7.10 (m, 4H,

ArH), 7.15-7.20 (m, 3H, ArH), 7.29-7.34 (m, 2H, ArH), 7.37 (dd,

1H, J = 1.35, 7.47 Hz, ArH), 7.42-7.47 (m, 2H, ArH), 7.56 (d, 1H, J = 7.44 Hz, ArH). 19F NMR

(282.4 MHz, CDCl3): δ = -113.6, -112.8, -110.3. 13C NMR (75.5 MHz, CDCl3): δ = 114.4 (d,

JF,C = 21.5 Hz, CH), 114.9 (d, JF,C = 21.6 Hz, CH), 115.3 (d, JF,C = 21.8 Hz, CH), 119.1, 122.6

(CH), 125.4 (d, JF,C = 3.37 Hz, C), 126.5 (CH), 127.3 (d, JF,C = 3.54 Hz, C), 128.9 (d, JF,C = 8.21

Hz, CH), 128.2 (C), 129.5 (d, JF,C = 8.28 Hz, CH), 130.8 (d, JF,C = 7.98 Hz, CH), 131.4 (C),

135.3 (d, JF,C = 3.25 Hz, C), 144.8, 144.9, 152.5 (C), 161.5 (d, JF,C = 248.8 Hz, C-F), 161.7 (d,

JF,C = 249.3 Hz, C-F), 162.0 (d, JF,C = 250.8 Hz, C-F), 194.6 (CO). IR (KBr): v = 3375, 3059,

2956, 2922, 2851 (w), 1697, 1592 (s), 1515, 1496, 1463 (m), 1430, 1410, 1402 (w), 1350 (m),

1328, 1299, 1275, 1260 (w), 1220 (s), 1185 (m), 1158 (s), 1143, 1094, 1070, 1012 (m), 964, 950,

935, 908, 871, 857 (w), 827, 812, 799 (s), 787, 748, 740 (m), 722, 712, 700, 661, 620 (w), 569,

557, 538 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 412 ([M]+, 100), 395 (11), 288 (13). HRMS

(EI, 70 eV): calcd for C27H15F3O [M]+,�� ! '�%��)�34,�� !9!

2,3,5-Tris (3-(trifluoromethyl)phenyl)-1H-inden-1-one (14g): Starting with 14 (80 mg, 0.22

mmol), Pd(PPh3)4 (13 mg, 5mol%), 1,4-dioxane (5 mL),

K2CO3 (2 M, 1 mL) and 3-(trifluoromethyl)phenylboronic

acid 3g (137 mg, 0.72 mmol), 14g was isolated as a

brownish yellow solid (96 mg, 78%). reaction �

��

��

��

��

temperature: 70°C for 6 h. Mp.155-156°C. 1H NMR (300 MHz, CDCl3): δ = 7.20 (d, 1H, J =

1.17 Hz, ArH), 7.31-7.44 (m, 4H, ArH), 7.48 (dd, 2H, J = 1.17, 7.49 Hz, ArH), 7.52-7.66 (m, 7H,

ArH), 7.71 (brs, 1H, ArH). 19F NMR (282.4 MHz, CDCl3): δ = -63.1, -63.0, -62.7. 13C NMR

(75.5 MHz, CDCl3): δ = 120.4 (CH), 123.5 (q, JF,C = 272.7 Hz, CF3), 123.7 (q, JF,C = 272.0 Hz,

CF3), 123.8 (q, JF,C = 271.3 Hz, CF3), 123.9 (q, JF,C = 3.81 Hz, CH), 124.1 (CH), 124.9 (q, JF,C =

3.62 Hz, CH), 125.2 (q, JF,C = 3.50 Hz, CH), 125.3 (q, JF,C = 3.83 Hz, CH), 126.5 (q, JF,C = 3.82

Hz, CH), 126.7 (q, JF,C = 3.90 Hz, CH), 128.6, 128.8, 129.6, 129.9, 130.5 (CH), 130.7 (C), 130.6

(q, JF,C = 22.6 Hz, C-CF3), 130.7 (q, JF,C = 22.4 Hz, C-CF3), 130.6 (q, JF,C = 24.8 Hz, C-CF3),

131.6 (CH), 132.7, 132.9 (C), 133.1 (CH), 140.8, 145.4, 145.7, 154.1(C), 194.7 (CO). IR (KBr):

v� = 3390, 3065, 2922, 2850 (w), 1706, 1600 (m), 1483, 1469 (w), 1438, 1429, 1361 (m), 1327,

1314 (s), 1303, 1283, 1241 (m), 1212 (w), 1182, 1162, 1112, 1098, 1067 (s), 1031 (m), 999, 955,

917, 907, 895, 849, 817 (m), 798 (s), 782, 769, 738 (m), 698, 689 (s), 677, 654 (m), 636, 621,

601, 533 (w) cm1. GC-MS (EI, 70 eV): m/z (%) = 562 ([M]+, 100), 493 (16). HRMS (EI, 70 eV):

calcd for C30H15F9O [M]+,�� !'9�9%��)�34,�� !'9�9

Synthesis of 3-aryl-2,5-dibromo-1H-inden-1-ones 15a-g:

2,5-Dibromo-3-phenyl-1H-inden-1-one (15a): Starting with 13 (100 mg, 0.27 mmol),

Pd(PPh3)4 (9 mg, 3 mol%), 1,4-dioxane (5 mL), K3PO4 (86 mg, 0.41

mmol) and phenylboronic acid 3i (33 mg, 0.27 mmol), 15a was isolated as

a brownish yellow solid (82 mg, 83%). reaction temperature: 45°C for 9 h.

Mp.108-110 °C. 1H NMR (300 MHz, CDCl3): δ = 7.19-7.20 (m, 1H, ArH),

7.32-7.37 (m, 2H, ArH), 7.45-7.57 (m, 5H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 119.1 (C),

124.7, 128.1 (CH), 128.5, 128.8 (C), 128.9 (CH), 130.5 (C), 130.6, 131.6 (CH), 146.3, 155.8 (C),

188.6 (CO). IR (KBr): v = 3422, 3087, 3062, 2921, 2850 (w), 1728 (s), 1681 (w), 1599, 1557

(m), 1498 (w), 1485, 1442, 1397, 1342 (m), 1299, 1282 (w), 1266 (m), 1190 (w), 1176, 1149,

1098, 1076, 1051, 1028 (m), 1000, 979, 966 (w), 931, 917, 875, 833, 814 (m), 785 (w), 769, 755,

714 (m), 688 (s), 663, 634, 611, 586 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 366 [(M+H), 81Br, 81Br]+, 51), 364 [(M+H), 79Br, 81Br]+, 100), 362 [(M+H), 79Br, 79Br]+, 51), 285 (27), 176 (51).

HRMS (EI, 70 eV): calcd for C15H8Br2O [M, 81Br, 81Br]+ ,�� ##'��%��)�34,�� ##'#��7/�74�

for C15H8Br2O [(M, 79Br, 81Br]+,�� #'� !%� �)�34,�� #'��7/�74� �)��15H8Br2O [M, 79Br, 79Br]+,�� #'� �%��)�34,�� #9368.

��

2,5-Dibromo-3-(4-tert-butylphenyl)-1H-inden-1-one (15b): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (9 mg, 3mol%), 1,4-dioxane (5 mL), K3PO4 (86 mg,

0.41mmol) and 4-tert-butylphenylboronic acid 3c (49 mg, 0.27 mmol),

15b was isolated as a brownish yellow solid (98 mg, 86%). reaction


CDCl3): δ = 1.32 (s, 9H, 3CH3), 7.26-7.38 (m, 3H, ArH), 7.48-7.55 (m,

4H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 31.2 (3CH3), 35.1, 118.5 (C), 124.5, 124.8, 125.9

(CH), 127.6 (C), 128.0 (CH), 128.6, 128.7 (C), 131.5 (CH), 146.3, 154.2, 155.8 (C), 188.7 (CO).

IR (KBr): v = 3427, 3088, 3028, 2960, 2903, 2865 (w), 1720 (s), 1682 (w), 1600, 1592, 1564

(m), 1495, 1463 (w), 1447 (m), 1400, 1362, 1339 (m), 1309 (w), 1288, 1271, 1190, 1176 (w),

1155, 1106, 1092, 1047, 1016 (m), 929 (s), 878 (m), 849 (w), 834, 811 (s), 770 (m), 746 (w),

717, 686, 632 (s), 588 (w), 550 (s) cm-1. GC-MS (EI, 70 eV): m/z (%) = 420 [(M+H), 79Br, 81Br]+, 49), 418 [(M+H), 79Br, 79Br]+, 24), 405 (100), 377 (17), 202 (11). HRMS (EI, 70 eV):

calcd for C19H16Br2O [(M, 79Br, 81Br]+,��' '��!%��)�34,��' '��9��7/�74��)��19H16Br2O [M, 79Br, 79Br]+,��9 '� ��%��)�34,��9 '�9��

2,5-Dibromo-3-(3-chlorophenyl)-1H-inden-1-one (15c): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (9 mg, 3 mol%), 1,4-dioxane (5 mL), K3PO4 (86 mg,

0.41 mmol) and 3-chlorophenylboronic acid 3n (42 mg, 0.27 mmol),

15c was isolated as a brownish yellow solid (87 mg, 80%). reaction


CDCl3): δ = 7.15 (d, 1H, J = 1.05 Hz, ArH), 7.35-7.45 (m, 5H, ArH), 7.51-7.52 (m, 1H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 120.8 (C), 124.5, 125.0, 126.2, 128.0 (CH), 128.1, 129.0 (C),

130.3, 130.6, 131.8 (CH), 132.3, 135.1, 145.9, 154.3 (C), 188.2 (CO). IR (KBr): v = 3415, 3064,

2918, 2849, 2156, 2137 (w), 1721 (s), 1682 (w), 1598, 1585, 1553 (m), 1519, 1504 (w), 1469,

1446, 1420, 1397, 1336 (m), 1302 (w), 1272 (m), 1221, 1179, 1166, 1152 (w), 1097, 1090, 1080,

1050 (m), 997 (w), 950 (m), 909 (w), 884, 834, 817 (m), 786 (s), 767 (m), 746, 732 (w), 712 (m),

705 (s), 682 (m), 665 (w), 649, 638 (m), 618, 599 (w), 588 (m) cm-1. GC-MS (EI, 70 eV): m/z

(%) = 400 [(M+H), 81Br, 81Br]+, 63), 398 [(M+H), 79Br, 81Br]+, 100), 396 [(M+H), 79Br, 79Br]+,

43), 319 (33), 210 (29), 174 (20). HRMS (EI, 70 eV): calcd for C15H7Br2ClO [M, 81Br, 81Br]+:

�'' #�!�#%� �)�34,� �'' #�!9�� 7/�74� �)�� 15H7Br2ClO [M, 79Br, 81Br]+,� �'9 #�� %� �)�34,�

397.85271, calcd for C15H7Br2ClO [M, 79Br, 79Br]+,��'� #�� 9%��)�34,��'� #��!�

��

2,5-Dibromo-3-(3-(trifluoromethyl)phenyl)-1H-inden-1-one (15d): Starting with 13 (100 mg,

0.27 mmol), Pd(PPh3)4 (9 mg, 3 mol%), 1,4-dioxane (5 mL), K3PO4

(86 mg, 0.41 mmol) 3-(trifluoromethyl)phenylboronic acid 3g (51

mg, 0.27 mmol), 15d was isolated as a brownish yellow solid (94 mg,

80%). reaction temperature: 45°C for 9 h. Mp.111-113°C. 1H NMR

(300 MHz, CDCl3): δ = 7.12 (d, 1H, J = 0.96 Hz, ArH), 7.35-7.42 (m,

2H, ArH), 7.61-7.74 (m, 3H, ArH), 7.81 (brs, 1H, ArH). 19F NMR (282.4 MHz, CDCl3): δ = -

62.8. 13C NMR (75.5 MHz, CDCl3): δ = 123.6 (q, JF,C = 272.8 Hz, CF3), 124.4 (CH), 125.0 (q,

JF,C = 3.85 Hz, CH), 125.1 (CH), 127.2 (q, JF,C = 3.56 Hz, CH), 128.1, 129.1 (C), 129.7, 131.3

(CH), 131.5 (C), 131.6 (q, JF,C = 32.80 Hz, C-CF3), 132.0 (CH), 145.8, 154.2 (C), 188.1 (CO). IR

(KBr): v = 3413, 3074, 2959, 2929, 2854 (w), 1716 (m), 1582, 1614 (w), 1595, 1586, 1556 (m),

1491(w), 1449, 1428, 1404, 1345 (m), 1326 (s), 1296, 1265 (w), 1250 (m), 1182 (w), 1165, 1150

(m), 1122, 1094, 1073, 1054 (s), 934, 926, 880, 861, 833, 818 (m), 800 (s), 766, 718, 703 (m),

697 (s), 677, 651, 622, 600, 585 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 434 [(M+H), 81Br, 81Br]+, 48), 432 [(M+H), 79Br, 81Br]+, 100), 430 [(M+H), 79Br, 79Br]+, 51), 351 (35), 244 (36).

HRMS (EI, 70 eV): calcd for C16H7F3Br2O [M, 81Br, 81Br]+,�� #9 '�%��)�34,�� #99!��7/�74�

for C16H7F3Br2O [M, 79Br, 81Br]+,� �� #9#'#%� �)�34,� �� #9#9#�� 7/�74� �)�� 16H7F3Br2O [M, 79Br, 79Br]+,��' ##�!�%��)�34,��' ##! �

2,5-Dibromo-3-(4-(trifluoromethoxy)phenyl)-1H-inden-1-one (15e): Starting with 13 (100

mg, 0.27 mmol), Pd(PPh3)4 (9 mg, 3 mol%), 1,4-dioxane (5 mL),

K3PO4 (86 mg, 0.41 mmol) and 4-(trifluoromethoxy)phenylboronic

acid 3p (56 mg, 0.27 mmol), 15e was isolated as a brownish yellow

solid (95 mg, 78%). reaction temperature: 45°C for 9 h. Mp.113-

115°C. 1H NMR (300 MHz, CDCl3): δ = 7.18-7.19 (m, 1H, ArH),

7.32-7.38 ((m, 4H, ArH), 7.61 (d, 2H, J = 8.85 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): δ = -

57.6. 13C NMR (75.5 MHz, CDCl3): δ = 118.8 (C), 119.4 (q, JF,C = 259.6 Hz, OCF3), 120.2,

123.5, 123.9 (CH), 127.2, 127.9, 128.0 (C), 128.9, 130.8 (CH), 144.9, 149.5, 153.3 (C), 187.2

(CO). IR (KBr): v = 3024, 3089, 2921, 2850 (w), 1729, 1609, 1597, 1590, 1504 (m), 1446,1399,

1342 (w), 1301 (m), 1246, 1205, 1149, 1116, 1049, 1052, 1017 (s), 969, 953 (w), 925 (m), 887

(w), 832, 816, 802, 765 (m), 732 (w), 717, 688 (m), 666, 644, 631 (w), 619 (m), 537 (w) cm-1.

GC-MS (EI, 70 eV): m/z (%) = 450 ([(M+H), 81Br, 81Br]+, 50), 448 ([(M+H), 79Br, 81Br]+, 100),

��

446 ([(M+H), 79Br, 79Br]+, 51), 367 (29), 260 (21). HRMS (EI, 70 eV): calcd for C16H7F3Br2O2

[M, 81Br, 81Br]+,� ��' #9�#�%� �)�34,� ��' #9�9!�� 7/�74� �)�� 16H7F3Br2O2 [M, 79Br, 81Br]+:

��9 #9�#'%� �)�34,� ��9 #9�� 7/�74� �)�� 16H7F3Br2O2 [M, 79Br, 79Br]+,� �� #9�'�%� �)�34,�

445.87555.

2,5-Dibromo-3-p-tolyl-1H-inden-1-one (15f): Starting with 13 (100 mg, 0.27 mmol), Pd(PPh3)4

(9 mg, 3 mol%), 1,4-dioxane (5 mL), K3PO4 (86 mg, 0.41 mmol) and

p-tolylboronic acid 3e (37 mg, 0.27 mmol), 15f was isolated as a

brownish yellow solid (88 mg, 86%). reaction temperature: 45°C for 9 h.

Mp.129-131°C. 1H NMR (300 MHz, CDCl3): δ = 2.38 (s, 3H, CH3), 7.21-

7.22 (m, 1H, ArH), 7.29 (d, 2H, J = 8.07 Hz, ArH), 7.33-7.37 (m, 2H,

ArH), 7.26 (d, 2H, J = 8.19 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ =

21.7 (CH3), 118.5 (C), 124.6, 124.7 (CH), 127.7 (C), 128.1 (CH), 128.6, 128.7 (C), 129.6, 131.5

(CH), 141.2, 146.3, 155.9 (C), 188.6 (CO). IR (KBr): v = 3424, 3089, 3027, 2915, 2850 (w),

1729 (s), 1599, 1590, 1564, 1556, 1444 (m), 1398 (w), 1343, 1289, 1270, 1184, 1150, 1097,

1053 (m), 1019 (w), 928, 880, 835 (m), 810 (s), 779 (w), 765, 720, 715, 687 (m), 654 (w), 631,

588 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 380 ([(M+H), 81Br, 81Br]+, 50), 378 ([(M+H), 79Br, 81Br]+, 100), 376 ([(M+H), 79Br, 79Br]+, 52), 297 (25), 189 (50). HRMS (EI, 70 eV): calcd for

C16H10Br2O [M, 81Br, 81Br]+,� �9' '!��!%� �)�34,� �9' '!�99�� 7/�74� �)�� 16H10Br2O [M, 79Br, 81Br]+,��99 '!9��%��)�34,��99 '!9�'��7/�74��)��16H10Br2O [M, 79Br, 79Br]+,��9� '!'�'%��)�34,�

375.90918.

2,5-Dibromo-3-(4-methoxyphenyl)-1H-inden-1-one (15g): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (9 mg, 3 mol%), 1,4-dioxane (5 mL), K3PO4 (86 mg,

0.41 mmol) and 4-methoxyphenylboronic acid 3h (41 mg, 0.27 mmol),

15g was isolated as a brownish yellow solid (99 mg, 92%). reaction


δ = 3.84 (s, 3H, OCH3), 6.70 (d, 2H, J = 8.88 Hz, ArH), 7.26 (d, 1H, J =

0.93 Hz, ArH), 7.32-7.36 (m, 2H, ArH), 7.56 (d, 2H, J = 8.85 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 55.5 (OCH3), 114.4 (CH), 117.8, 122.8 (C), 124.5, 124.7

(CH), 128.5, 128.8 (C), 130.0, 131.5 (CH), 146.3, 155.5, 161.5 (C), 188.7 (CO). IR (KBr): v =

3409, 3070, 3025, 2985, 2955, 2921, 2850, 2282, 2035 (w), 1715, 1597 (s), 1567, 1555 (m),

1503 (s), 1470 (w), 1444, 1419 (m), 1401(w), 1341, 1307, 1275 (m), 1257 (s), 1193 (w), 1173

��

(s), 1152, 1118, 1102, 1091, 1052 (m), 1017 (s), 954 (w), 927 (m), 873 (w), 822, 813 (s), 782,

766, 732, 712, 690, 632, 621, 576 (m), 528 (s) cm-1. GC-MS (EI, 70 eV): m/z (%) = 396

([(M+H), 81Br, 81Br]+, 52), 394 ([(M+H), 79Br, 81Br]+, 100), 392 ([(M+H), 79Br, 79Br]+, 53), 313

(10), 191 (09), 163 (34). HRMS (EI, 70 eV): calcd for C16H10Br2O2 [M, 81Br, 81Br]+,��'� '!!��%�

found: 395.90004, calcd for C16H10Br2O2 [M, 79Br, 81Br]+: 393.'!�� %� �)�34,��'� '!� ��7/�74�

for C16H10Br2O2 [M, 79Br, 79Br]+,��'� '!��%��)�34,��'� '!�9!

Synthesis of symmetrical 2,3-diaryl-5-bromo-1H-inden-ones 16a-g:

�5-Bromo-2,3-bis(4-ethylphenyl)-1H-inden-1-one (16a): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane (5mL), K3PO4

(172 mg, 0.81 mmol) and 4-ethylphenylboronic acid 3b (82 mg,

0.55 mmol), 16a was isolated as a brownish yellow solid (100 mg,


(300 MHz, CDCl3): δ = 1.15 (t, 3H, J = 7.56 Hz, CH3), 1.23 (t, 3H,

J = 7.56 Hz, CH3), 2.55 (q, 2H, J = 7.59 Hz, CH2), 2.64 (q, 2H, J = 7.59 Hz, CH2), 7.03 (d, 2H, J

= 8.43 Hz, ArH), 7.14 (d, 2H, J = 8.31 Hz, ArH), 7.19-7.24 (m, 5H, ArH), 7.33-7.38 (m, 2H,

ArH). 13C NMR (75.5 MHz, CDCl3): δ = 14.1, 14.2 (CH3), 27.7, 28.8 (CH2), 123.9, 124.6, 127.7

(CH), 128.1 (C), 128.4, 128.5 (CH), 129.5, 129.6 (C), 129.9, 131.4 (CH), 132.9, 144.1, 145.9,

147.5, 153.6 (C), 195.0 (CO). IR (KBr): v = 3389, 3068, 3034, 2961, 2923, 2851, 1737, 1731

(w), 1702 (s), 1590, 1576, 1501, 1454, 1411, 1350 (m), 1328 (w), 1259, 1174, 1116, 1095, 1068

(m), 1047, 1017 (s), 961, 953 (w), 930, 883, 862, 837(m), 819 (s), 801 (m), 765, 743, 735, 718

(w), 699, 661, 648, 638, 582, 564, 527 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 416 ([M, 79Br]+,

100), 387 (36), 263 (23). HRMS (EI, 70 eV): calcd for C25H21BrO [M, 79Br]+,�� !99!�%��)�34,�

416.07706.

5-Bromo-2,3-bis(4-tert-butylphenyl)-1H-inden-1-one (16b): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane (5 mL), K3PO4

(172 mg, 0.81 mmol) and 4-tert-butylphenylboronic acid 3c (98

mg, 0.55 mmol), 16b was isolated as a brownish yellow solid

(107 mg, 83%). reaction temperature: 60°C for 6 h. Mp188-

190°C. 1H NMR (300 MHz, CDCl3): δ = 1.22 (s, 9H, 3CH3),

1.29 (s, 9H, 3CH3), 7.15 (d, 2H, J = 8.49 Hz, ArH), 7.19-7.26

(m, 5H, ArH), 7.34-7.39 (m, 4H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 31.3 (6CH3), 34.7,

�

�

��

34.9 (C), 123.9, 124.7, 125.1, 125.9 (CH), 127.4 (C), 128.2 (CH), 129.3, 129.5 (C), 129.6, 131.3

(CH), 132.8, 147.7, 151.0, 152.8, 153.5 (C), 195.7 (CO). IR (KBr): v = 3099, 3058, 3046, 3027,

2960, 2928, 2903, 2865 (m), 1707 (s), 1602, 1589, 1577 (m), 1556, 1459 (w), 1459, 1396, 1362,

1349, 1262 (m), 1199, 1181, 1113, 1104, 1092 (w), 1069, 1050, 1014 (m), 975, 958 (w), 933,

865, 857, 850, 841, 829 (m), 818 (s), 779, 739, 730 (m), 654, 635, 625, 566 (w), 559 (s) cm-1.

GC-MS (EI, 70 eV): m/z (%) = 474 ([M, 81Br]+, 75), 472 ([M, 79Br]+, 73), 459 (100), 457 (98),

194 (16). HRMS (EI, 70 eV): calcd for C29H29BrO [M, 81Br]+,� �9� ��9�#%� �)�34,� �9� ��#!�%�

calcd for C29H29BrO [M, 79Br]+,��9� ��' �%��)�34,��9� ��'��

5-Bromo-2,3-bis(3-methoxyphenyl)-1H-inden-1-one (16c): Starting with 13 (100 mg, 0.27


(172 mg, 0.81 mmol) and 3-methoxyphenylboronic acid 3o (83

mg, 0.55 mmol), 18c was isolated as a brownish yellow solid (86

mg, 75%). reaction temperature: 60°C for 6 h. Mp.164-166°C. 1H

NMR (300 MHz, CDCl3): δ = 3.59 (s, 3H, OCH3), 3.65 (s, 3H,

OCH3), 6.72-6.89 (m, 6H, ArH), 7.10 (t, 1H, J = 7.68 Hz, ArH), 7.18-7.20 (m, 1H, ArH), 7.31 (t,

1H, J = 7.90 Hz, ArH), 7.33-7.39 (m, 2H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 55.1, 55.3

(OCH3), 113.7, 114.4, 115.0, 115.3, 120.6, 122.5, 124.1, 124.8 (CH), 128.4 (C), 129.2 (CH),

129.3 (C), 130.2 (CH), 131.5 (C), 131.7 (CH), 133.3, 133.5, 147.2, 154.2, 159.2, 159.9 (C),

195.1 (CO). IR (KBr): v = 3400, 3070, 2999, 2954, 2919, 2849, 2833 (w), 1709, 1590, 1575 (s),

1479, 1453,1426 (m), 1401 (w), 1348, 1329, 1286 (m), 1263 (w), 1228 (m), 1171, 1132, 1093

(m), 1042 (s), 960 (m), 929, 919 (w), 887, 879, 832 (m), 786, 772 (s), 721, 688 (s), 647 (m), 606

(w), 593 (m), 566, 556 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 422 ([M, 81Br]+, 71), 420 ([M, 79Br]+, 100), 389 (15), 298 (15), 226 (36). HRMS (EI, 70 eV): calcd for C23H17BrO3 [M, 81Br]+:

�� !��%��)�34,�� !��9��7/�74��)��23H17BrO3 [M, 79Br]+,��! !�� %��)�34,��! !��9

5-Bromo-2,3-bis(4-fluorophenyl)-1H-inden-1-one (16d): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane (5 mL), K3PO4 (172

mg, 0.81 mmol) and 4-fluorophenylboronic acid 3j (77 mg, 0.55

mmol), 16d was isolated as a brownish yellow solid (84 mg, 78%).

reaction temperature: 60°C for 6 h. Mp.184-185°C. 1H NMR (300

MHz, CDCl3): δ = 6.90 (t, 2H, J = 8.61 Hz, ArH), 7.07 (t, 2H, J =

8.61 Hz, ArH), 7.13-7.18 (m, 3H, ArH), 7.24-7.29 (m, 2H, ArH), 7.34-7.41 (m, 2H, ArH). 19F

� ��

NMR (282.4 MHz, CDCl3): δ = -112.3, -109.8. 13C NMR (75.5 MHz, CDCl3): δ = 115.4 (d, JF,C

= 21.7 Hz, CH), 116.4 (d, JF,C = 21.9 Hz, CH), 124.2, 124.6 (CH), 126.1 (d, JF,C = 3.56 Hz, C),

127.9 (d, JF,C = 3.49 Hz, C), 128.5, 129.1 (C), 130.4 (d, JF,C = 8.31 Hz, CH), 131.8 (d, JF,C = 7.71

Hz, CH), 131.9 (CH), 132.5, 146.9, 152.9 (C), 162.9 (d, JF,C = 249.3 Hz, CF), 163.2 (d, JF,C =

251.2 Hz, CF), 194.9 (CO). IR (KBr): v = 3407, 3076, 3047, 2922, 2852, 2158, 1895 (w), 1709

(s), 1596, 1584, 1575 (s), 1511(m), 1499 (s), 1456, 1404, 1351, 1330, 1301 (m), 1278 (w), 1224

(s), 1178 (m), 1159 (s), 1093, 1065, 1050, 1015, 941, 927, 880, 864, 856, 845 (m), 825, 818 (s),

800, 776, 744, 732, 694, 662, 631, 619, 592, 567(m), 546, 532 (s) cm-1. GC-MS (EI, 70 eV): m/z

(%) = 398 ([(M+H), 81Br]+, 98), 396 ([(M+H), 79Br]+, 100), 317 (52), 288 (79). HRMS (EI, 70

eV): calcd for C21H11F2BrO [M, 81Br]+,� �'9 ''��%� �)�34,� �'9 ''�� 7/�74� �)��21H11F2BrO

[M, 79Br]+,��'� ''��'%��)�34,��'� ''��

5-Bromo-2,3-bis(3-(trifluoromethyl)phenyl)-1H-inden-1-one (16e): Starting with 13 (100 mg,

0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane (5 mL),

K3PO4 (172 mg, 0.81 mmol) and 3-(trifluoromethyl)phenylboronic

acid 3g (104 mg, 0.55 mmol), 16e was isolated as a brownish

yellow solid (105 mg, 77%). reaction temperature: 60°C for 6 h.

Mp.150-152°C. 1H NMR (300 MHz, CDCl3): δ = 7.15 (d, 1H, J =

1.02 Hz, ArH), 7.32-7.57 (m, 9H, ArH), 7.15 (brs, 1H, J = 7.68 Hz, ArH). 19F NMR (282.4 MHz,

CDCl3): δ = -63.1, -63.0. 13C NMR (75.5 MHz, CDCl3): δ = 123.3 (q, JF,C = 272.8 Hz, CF3),

123.4 (q, JF,C = 272.5 Hz, CF3), 124.7, 124.8 (CH), 125.1 (q, JF,C = 3.54 Hz, CH), 125.2 (q, JF,C =

3.58 Hz, CH), 126.6 (q, JF,C = 3.69 Hz, CH), 126.7 (q, JF,C = 3.76 Hz, CH), 128.8 (C), 128.9,

129.9 (CH), 130.4 (C), 130.9 (q, JF,C = 32.5 Hz, C-CF3), 131.5 (CH), 132.0 (q, JF,C = 32.9 Hz, C-

CF3), 132.5 (CH), 132.5, 132.8 (C), 133.1 (CH), 146.2, 153.5 (C), 194.0 (CO). IR (KBr): v =

3070, 2923, 2851, 2143 (w), 1704 (s), 1600, 1583 (m), 1479 (w), 1442 (m), 1403 (w), 1354 (m),

1324, 1313, 1295 (s), 1276, 1261, 1163 (m), 1120, 1097, 1068 (s), 1051 (m), 1000 (w), 951 (m),

932 (w), 911, 881, 861, 840 (m), 806 (s), 781, 769, 740, 720 (m), 698 (s), 672, 658 (m), 650,

642, 631, 621 (w), 595 (m), 530 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 498 ([(M+H), 81Br]+,

98), 496 ([(M+H), 79Br]+, 100), 417 (20), 397 (22), 320 (30). HRMS (EI, 70 eV): calcd for

C23H11F6BrO [M, 81Br]+,� �'9 '#9��%� �)�34,� �'9 '# �9�� 7/�74� �)�� 23H11F6BrO [M, 79Br]+:

�'� '#'�!%��)�34,��'� '##'#

��

5-Bromo-2,3-bis(4-methoxyphenyl)-1H-inden-1-one (16f): Starting with 13 (100 mg, 0.27

mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane (5 mL),

K3PO4 (172 mg, 0.81 mmol) and 4-methoxyphenylboronic

acid 3h (83 mg, 0.55 mmol), 18f was isolated as a brownish

yellow solid (98 mg, 85%). reaction temperature: 60°C for 6 h.

Mp.126-128°C. 1H NMR (300 MHz, CDCl3): δ = 3.72 (s, 3H,

OCH3), 3.79 (s, 3H, OCH3), 6.75 (d, 2H, J = 8.91 Hz, ArH),

6.88 (d, 2H, J = 8.85 Hz, ArH), 7.16 (d, 2H, J = 8.94 Hz, ArH), 7.21 (brs, 1H, ArH), 7.25 (d, 2H,

J = 8.82 Hz, ArH), 7.33-7.34 (m, 2H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 55.2, 55.34

(OCH3), 113.1, 113.8 (CH), 122.9 (C), 123.2, 123.8 (CH), 124.6, 128.1, 129.6 (C), 130.1, 131.2,

131.3 (CH), 132.2, 147.6, 152.6, 159.4, 160.5 (C), 195.7 (CO). IR (KBr): v = 3409, 3071, 3026,

2987, 2956, 2920, 2850, 1898 (w), 1715, 1597, 1555, 1503, 1444 (s), 1420, 1401, 1342, 1307,

1275 (m), 1257, 1173 (s), 1152, 1118, 1103, 1091, 1052 (m), 1017 (s), 954 (w), 927 (m), 872

(w), 821 (s), 782, 766, 732, 712, 690, 632, 621, 588, 576 (m), 528 (s) cm-1. GC-MS (EI, 70 eV):

m/z (%) = 422 ([M, 81Br]+, 98), 420 ([M, 79Br]+, 100), 405 (12), 255 (13), 226 (26). HRMS (EI,

70 eV): calcd for C23H17BrO3 [M, 81Br]+,� �� !��%� �)�34,�� !�� !�� 7/�74� �)��23H17BrO3

[M, 79Br]+,��! !�� %��)�34,��! !��9

5-Bromo-2,3-bis(4-chlorophenyl)-1H-inden-1-one (16g): Starting with 13 (100 mg, 0.27


(172 mg, 0.81 mmol) and 4-chlorophenylboronic acid 3f (86 mg,

0.55 mmol), 16g was isolated as a brownish yellow solid (102 mg,


(300 MHz, CDCl3): δ = 7.09 (d, 2H, J = 8.64 Hz, ArH), 7.14-7.22

(m, 5H, ArH), 7.33-7.40 (m, 4H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 124.4, 124.6 (CH),

128.4, 128.6 (C), 128.7 (CH), 129.1 (C), 129.6, 129.7 (CH), 130.3 (C), 131.2, 132.0 (CH), 132.5,

134.5, 135.9, 146.6, 153.1 (C), 194.5 (CO). IR (KBr): v = 3419, 3089, 3075, 3063, 2919, 2850

(w), 1715 (s), 1601, 1586, 1574, 1557, 1484, 1454, 1395, 1348 (m), 1330, 1305, 1282, 1265,

1210 (w), 1174, 1150 (m), 1087 (s), 1063, 1045 (m), 1013 (s), 974, 955, 946 (w), 929, 877, 858,

832, 821 (m), 812 (s), 776 (m), 740 (w), 726 (m), 715, 707, 688, 647, 630, 626, 618, 589 (w) cm-

1. GC-MS (EI, 70 eV): m/z (%) = 430 ([M, 81Br, 35Cl, 35Cl]+, 100), 428 ([(M+H), 79Br, 35Cl, 35Cl]+, 61), 395 (20), 314 (30), 286 (30), 250 (53). HRMS (EI, 70 eV): calcd for C21H11Cl2BrO

[M, 79Br, 35Cl, 35Cl]+: 427.93648, found: 427.93635.

��

General procedure (B) for Suzuki cross-coupling reactions of brominated indenone (13): The

reaction was carried out in a pressure tube. To a 1,4-dioxane suspension (3-5 mL) of the

brominated indenone, Pd(PPh3)4 or Pd(PPh3)2Cl2 (5 mol%) and of the Ar1B(OH)2 (1.0 equiv. per

cross-coupling), K3PO4 (1.5 equiv. per cross coupling) or an aqueous solution of K2CO3 (2 M, 1

mL) was added. The mixture was heated at the indicated temperature (45°C) under Argon

atmosphere for the indicated period of time (9 h) and cooled to room temperature. Then

Ar2B(OH)2 (1.0-1.1 equiv. per cross-coupling) was added and reaction mixture was further

heated (6 h) at 60°C. The reaction mixture was again cooled to room temperature and diluted

with water and extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were dried

(Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by flash


Synthesis of unsymmetrical 2,3-diaryl-5-bromo-1H-inden-ones 17a-c:

5-Bromo-3-(4-ethylphenyl)-2-(4-methoxyphenyl)-1H-inden-1-one (17a): Starting with 13

(100 mg, 0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%), was added

1,4-dioxane (5 mL), K3PO4 (172 mg, 0.81 mmol), 4-

ethylphenylboronic acid 3b (40 mg, 0.27 mmol) and 4-

methoxyphenylboronic acid 3h (41 mg, 0.27 mmol) following the

general procedure B, 17a was isolated as a brownish yellow

solid (92 mg, 80%). reaction temperature: at 45°C for 9h, at 60°C for 6 h. Mp.120-122°C. 1H

NMR (300 MHz, CDCl3): δ = 1.21 (t, 3H, J = 7.59 Hz, CH3), 2.63 (q, 2H, J = 7.62 Hz, CH2),

3.71 (s, 3H, OCH3), 6.73 (d, 2H, J = 8.91 Hz, ArH), 7.13-7.22 (m, 7H, ArH), 7.31-7.34 (m, 2H,

ArH). 13C NMR (62.9 MHz, CDCl3): δ = 15.2 (CH3), 28.8 (CH2), 55.2 (OCH3), 113.7 (CH),

122.8 (C), 123.8, 124.4 (CH), 128.2 (C), 128.4, 128.5 (CH), 129.5, 129.6 (C), 131.2, 131.3 (CH),

132.5, 145.8, 147.6, 152.8, 159.4 (C), 195.7 (CO). IR (KBr): v = 3419, 3079, 2997, 2962, 2925,

2852, 2836 (w), 1709 (s), 1600, 1589, 1577, 1514, 1500, 1453, 1444 (m), 1400, 1349, 1329,

1293 (w), 1248, 1183 (s), 1049, 1117, 1093 (w), 1065, 1049, 1029, 1017 (m), 930 (s), 880, 852

(m), 838, 820 (s), 774 (m), 743, 733, 717 (w), 699 (m), 681, 660, 649, 632 (w), 582, 561, 540,

526 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 420 ([M, 81Br]+, 100), 418 ([M, 79Br]+, 96), 239

(19). HRMS (EI, 70 eV): calcd for C24H19BrO2 [M, 81Br]+,��! !��%��)�34,��! !�� #%�7/�74�

for C24H19BrO2 [M, 79Br]+,��# !� �'%��)�34,��# !� ��

��

5-Bromo-3-(4-chlorophenyl)-2-(4-ethylphenyl)-1H-inden-1-one (17b): Starting with 13 (100

mg, 0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%), was added 1,4-

dioxane (5 mL), K3PO4 (172 mg, 0.81 mmol), 4-

chlorophenylboronic acid 3f (42 mg, 0.27 mmol) and 4-

ethylphenylboronic acid 3b (40 mg, 0.27 mmol) following the

general procedure B, 17b was isolated as a brownish yellow solid

(92 mg, 79%). reaction temperature: at 45°C for 9h, at 60°C for 6 h. Mp.133-134°C. 1H NMR

(300 MHz, CDCl3): δ = 1.14 (t, 3H, J = 7.59 Hz, CH3), 2.54 (q, 2H, J = 7.59 Hz, CH2), 7.02-7.11

(m, 4H, ArH), 7.13 (brs, 1H, ArH), 7.23 (d, 2H, J = 8.57 Hz, ArH), 7.33-7.35 (m, 4H, ArH). 13C

NMR (75.5 MHz, CDCl3): δ = 15.2 (CH3), 28.7 (CH2), 124.2, 124.3 (CH), 127.2 (C), 127.9

(CH), 128.4, 129.2 (C), 129.4, 129.8, 129.9 (CH), 130.8 (C), 131.6 (CH), 133.8, 135.4, 144.6,

147.1, 152.0 (C), 195.1 (CO). IR (KBr): v = 3390, 3082, 3060, 3030, 2964, 2917, 2871, 2849

(w), 1705 (s), 1597, 1582, 1574 (m), 1508 (w), 1484, 1450, 1396, 1349, 1328 (m), 1259 (w),

1171, 1148 (m), 1120, 1108 (w), 1088 (s), 1068, 1047 (m), 1012 (s), 969, 951 (w), 930, 875,

860, 853 (m), 827, 819 (s), 779, 742, 733, 716, 692, 654, 637, 620, 589, 569, 534 (m) cm-1. GC-

MS (EI, 70 eV): m/z (%) = 426 ([M, 37Cl, 81Br]+, 26), 424 ([M, 35Cl, 81Br]+, 100), 422 ([M, 35Cl, 79Br]+, 76), 409 (33), 263 (28). HRMS (EI, 70 eV): calcd for C23H16BrClO [M, 35Cl, 79Br]+:

�� !! 9 %��)�34,�� !!��

5-Bromo-3-(4-chlorophenyl)-2-(4-methoxyphenyl)-1H-inden-1-one (17c): Starting with 13

(100 mg, 0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%), was added 1,4-

dioxane (5 mL), K3PO4 (172 mg, 0.81 mmol), 4-


methoxyphenylboronic acid 3h (41 mg, 0.27 mmol) following the

general procedure B, 17c was isolated as a brownish yellow solid

(95 mg, 82%). reaction temperature: at 45°C for 9h, at 60°C for 6 h. Mp.170-171°C. 1H NMR

(250 MHz, CDCl3): δ = 3.71 (s, 3H, OCH3), 6.74 (d, 2H, J = 8.43 Hz, ArH), 7.11-7.18 (m, 3H,

ArH), 7.23 (d, 2H, J = 8.10 Hz, ArH), 7.31-7.36 (m, 4H, ArH). 13C NMR (62.9 MHz, CDCl3): δ

= 54.2 (OCH3), 112.8 (CH), 121.2 (C), 123.1 (CH), 127.4, 128.1 (C), 128.4, 128.8 (CH), 129.9

(C), 130.3, 130.4 (CH), 132.2, 134.3, 146.2, 150.0, 158.6 (C), 194.3 (CO). IR (KBr): v = 3041,

3059, 3018, 2958, 2930, 2838 (w), 1709, 1600, 1576 (s), 1510, 1485, 1455, 1445 (m), 1416,

1407, 1396 , 1352 , 1329 (w), 1295 (m), 1251, 1174 (s), 1152, 1114 (w), 1090 (s), 1065, 1047

(m), 1024, 1013 (s), 974, 957, 946 (w), 929 (s), 879, 846 (m), 828, 812 (s), 779, 742, 734, 717,

��

691, 654 (m), 643, 632, 618, 590 (w), 566, 536 (s) cm-1. GC-MS (EI, 70 eV): m/z (%) = 426

([(M+H), 81Br, 35Cl]+, 100), 424 ([M+H), 79Br, 35Cl]+, 77), 267 (16), 239 (37). HRMS (EI, 70

eV): calcd for C22H14BrClO2 [M, 81Br, 35Cl]+,� �� '#�'9%� �)�34,� �� '#��!%� 7/�74� �)��

C22H14BrClO2 [M, 79Br, 35Cl]+: 423.'# !�%��)�34,��.98530.

Synthesis of unsymmetrical 2,3,5-triaryl-1H-inden-ones 18a-c and 19a,b:

2,5-Bis(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1H-inden-1-one (18a): Starting with 15g (78

mg, 0.199 mmol), Pd(PPh3)4 (11 mg, 5 mol%), 1,4-

dioxane (5 mL), K2CO3 (2 M, 1 mL) and 4-tert-

butylphenylboronic acid 3c (82 mg, 0.43 mmol),

following the general procedure A, 18a was isolated as

a brownish yellow solid (77 mg, 78%). reaction

temperature: 70°C for 6 h. Mp.188-190°C. 1H NMR

(300MHz, CDCl3): δ = 1.22 (s, 9H, 3CH3), 1.27 (s, 9H, 3CH3), 3.77 (s, 3H, OCH3), 6.85 (d, 2H,

J = 8.61 Hz, ArH), 7.15-7.23 (m, 4H, ArH), 7.29-7.44 (m, 8H, ArH), 7.52 (d, 1H, J = 8.54 Hz,

ArH). 13C NMR (62.9 MHz, CDCl3): δ = 30.2, 30.3 (CH3), 33.5, 33.6 (C), 54.3 (OCH3), 114.3,

120.3, 123.1 (CH), 123.1 (C), 125.1, 125.8, 126.9, 127.0 (CH), 128.0 (C), 129.6, 130.2 (CH),

132.2, 137.6, 146.2, 146.3, 149.5, 150.4, 153.0, 159.3 (C), 195.4 (CO). IR (KBr): v = 3033,

2958, 2923, 2855 (w), 1700, 1597 (s), 1510, 1499, 1463 (m), 1493, 1405, 1392 (w), 1352 (m),

1332, 1307, 1290, 1266 (w), 1248, 1175 (s), 1111, 1092, 1070 (m), 1040 (w), 1023 (s), 958, 948,

941, 931, 908, 896, 867, 856 (w), 821 (s), 808, 784, 740, 729, 690, 649 (m), 638, 629, 610 (w),

573, 543, 534 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 500 ([M]+, 100), 485 (70), 235 (21).

HRMS (EI, 70 eV): calcd for C36H36O2 [M]+,��!! �9!'#%��)�34,��!! �9��

3-(4-Chlorophenyl)-2,5-bis(4-ethylphenyl)-1H-inden-1-one (18b): Starting with 13 (100 mg,

0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane (5

mL), K3PO4 (262 mg, 1.23 mmol), 4-chlorophenylboronic

acid 3f (43 mg, 0.27 mmol) and 4-ethylphenylboronic

acid 3b (89 mg, 0.59 mmol) following the general

procedure B, 18b was isolated as a brownish yellow solid

(99 mg, 81%). reaction temperature: at 45°C for 9h, at

70°C for 6 h. Mp.133-134°C. 1H NMR (300 MHz, CDCl3): δ = 1.15 (t, 3H, J = 7.62 Hz, CH3),

1.19 (t, 3H, J = 7.62 Hz, CH3), 2.55 (q, 2H, J = 7.59 Hz, CH2), 2.61 (q, 2H, J = 7.59 Hz, CH2),

��

7.04 (d, 2H, J = 8.25 Hz, ArH), 7.12 (d, 2H, J = 8.28 Hz, ArH), 7.17-7.21 (m, 3H, ArH), 7.26-


MHz, CDCl3): δ = 14.2, 14.5 (CH3), 27.5, 27.6 (CH2), 119.0, 122.5, 126.1, 126.2 (CH), 126.6

(C), 126.7, 127.4 (CH), 128.1 (C), 128.2, 128.8, 129.0 (CH), 130.4, 132.5, 134.0, 136.6, 143.2,

143.7, 144.9, 145.8, 151.6 (C), 195.0 (CO). IR (KBr): v = 3391, 3024, 2961, 2926, 2870, 1907,

1789 (w), 1706, 1595 (s) 1515 (w), 1485, 1462, 1455 (m), 1410, 1373 (w), 1351 (m), 1260 (w),

1181, 1142 (m), 1087 (s), 1069, 1049 (m), 1012 (s), 963, 948, 935, 894, 862, 850 (w), 819 (s),

784, 741, 717 (m), 700, 670, 654, 638, 621, 571 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 448

([M]+, 100), 433 (18), 419 (16). HRMS (EI, 70 eV): calcd for C31H25ClO [M]+,� ��# ��##�%�

found: 448.15899.

3-(4-Chlorophenyl)-2,5-bis(4-methoxyphenyl)-1H-inden-1-one (18c): Starting with 13 (100

mg, 0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%), 1,4-dioxane

(5 mL), K3PO4 (262 mg, 1.23 mmol), 4-


ethylphenylboronic acid 3b (90 mg, 0.59 mmol) following

the general procedure B, 18c was isolated as a brownish

yellow solid (104 mg, 84%). reaction temperature: at 45°C

for 9h, at 70°C for 6 h. Mp.201-203°C. 1H NMR (250 MHz, CDCl3): δ = 3.81 (s, 3H, OCH3),

3.85 (s, 3H, OCH3), 6.74 (d, 2H, J = 8.80 Hz, ArH), 6.88 (d, 2H, J = 8.72 Hz, ArH), 7.13-7.18

(m, 3H, ArH), 7.26-7.36 (m, 5H, ArH), 7.42 (d, 2H, J = 8.70 Hz, ArH), 7.52 (d, 1H, J = 7.47 Hz,

ArH). 13C NMR (62.9 MHz, CDCl3): δ = 55.2 (OCH3), 55.4 (OCH3), 113.8, 114.3, 119.5 (CH),

122.8 (C), 123.5, 126.6, 128.3 (CH), 128.7 (C), 129.3, 130.0, 131.3 (CH), 131.5, 132.7, 133.0,

135.0, 146.1, 146.4, 151.7, 159.4, 160.0 (C), 196.2 (CO). IR (KBr): v = 3377, 3057, 3042, 3010,

2951, 2925, 2835 (w), 1697 (s), 1608 (w), 1591 (s), 1516 , 1486, 1462, 1455, 1442 (m), 1413,

1398, 1348, 1331, 1307 (w), 1286 (m), 1246, 1173 (s), 1141, 1087, 1071, 1039, 1013 (m), 936,

893, 850 (w), 836 (m), 822 (s), 811, 797, 786, 744, 738, 727, 718 (m), 699, 655, 621(w), 571,

562 (m) cm-1. GC-MS (EI, 70 eV): m/z (%) = 452 ([M, 35Cl]+, 100), 226 (12). HRMS (EI, 70

eV): calcd for C29H21ClO3 [M, 35Cl]+,�� 9�9%��)�34,�� #!�

��

2,3-Bis(4-fluorophenyl)-5-(3-methoxyphenyl)-1H-inden-1-one (19a): Starting with 16d (79

mg, 0.20 mmol), Pd(PPh3)4 (8 mg, 3 mol%), 1,4-dioxane (5 mL),

K2CO3 (2 M, 1 mL) and 3-methoxyphenylboronic acid 3o (33 mg,

0.22 mmol), following the general procedure A, 21a was isolated as

a yellow solid (74 mg, 88%). reaction temperature: 70°C for 6 h.

Mp.175-177°C. 1H NMR (300 MHz, CDCl3): δ = 3.78 (s, 3H,

OCH3), 6.84-6.94 (m, 3H, ArH), 6.99-7.10 (m, 4H, ArH), 7.14-7.21

(m, 3H, ArH), 7.26-7.35 (m, 3H, ArH), 7.41 (dd, 1H, J = 1.41, 7.44 Hz, ArH), 7.56 (d, 1H, J =

7.47 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): δ = -112.9, -110.4. 13C NMR (62.9 MHz,

CDCl3): δ = 55.4 (OCH3), 113.2, 113.3 (CH), 115.3 (d, JF,C= 21.5 Hz, CH), 116.3 (d, JF,C = 21.7

Hz, CH), 119.7, 120.4, 123.5 (CH), 126.5 (d, JF,C = 3.50 Hz, C), 127.7 (CH), 128.5 (d, JF,C = 3.53

Hz, C), 129.4 (C), 130.0 (CH), 130.5 (d, JF,C = 8.26 Hz, CH), 131.7 (d, JF,C = 8.11 Hz, CH),

132.3, 141.7, 145.7, 146.8, 153.6, 160.0 (C), 162.4 (d, JF,C = 248.6 Hz, C), 163.2 (d, JF,C = 250.3

Hz, C), 195.7 (CO). IR (KBr): v = 3393, 3066, 3034, 2919, 2850 (w), 1704, 1596 (s), 1738, 1731

(w), 1704 (s), 1667, 1651, 1644, 1633 (w), 1596 (s), 1575 (m), 1510, 1538 (w), 1510, 1495, 1463

(m), 1437, 1417, 1406 (w), 1351 (m), 1316, 1298, 1279, 1263, 1248 (w), 1223, 1211(s), 1186,

1171, 1160, 1154 (m), 1101, 1080, 1071, 1049, 1023, 965, 951, 944, 877(w), 849 (s), 838 (m),

816 (s), 800, 793 (w), 772 (s), 747, 736, 712, 696, 676 (m), 666, 629, 608 , 581(w), 568 (m),

548, 536 (s) cm-1. GC-MS (EI, 70 eV): m/z (%) = 424 ([M]+, 100). HRMS (EI, 70 eV): calcd for

C28H18F2O2 [M]+,�� '�%��)�34,�� '�

5-(4-Methoxyphenyl)-2,3-bis(4-(trifluoromethyl)phenyl)-1H-inden-1-one (19b): Starting

with 13 (100 mg, 0.27 mmol), Pd(PPh3)4 (15 mg, 5 mol%),

1,4-dioxane (5 mL), K3PO4 (172 mg, 0.81 mmol), 4-

(trifluoromethyl)phenylboronic acid 3q (102 mg, 0.54

mmol) and 4-methoxyphenylboronic acid 3h (42 mg, 0.27

mmol) following the general procedure B, 19b was isolated

as a yellow solid (124 mg, 86%). reaction temperature: at

60°C for 9h, at 70°C for 6 h. Mp.200-201°C. 1H NMR (300 MHz, CDCl3): δ = 3.77 (s, 3H,

OCH3), 6.89 (d, 2H, J = 8.76 Hz, ArH), 7.17 (s, 1H, ArH), 7.28 (d, 2H, J = 8.10 Hz, ArH), 7.41-

7.48 (m, 7H, ArH), 7.59 (d, 1H, J = 7.50 Hz, ArH), 7.65 (d, 2H, J = 8.13 Hz, ArH). 19F NMR

(282.4 MHz, CDCl3): δ = -62.8, -62.7. 13C NMR (62.9 MHz, CDCl3): δ = 55.4 (OCH3), 114.4,

120.2 (CH), 123.6 (q, JF,C = 272.6 Hz, CF3), 123.8 (q, JF,C = 270.3 Hz, CF3), 124.1 (CH), 125.2

��

(q, JF,C = 3.83 Hz, CH), 126.2 (q, JF,C = 3.75 Hz, CH), 127.4 (CH), 128.2 (C), 128.3, 128.9 (CH),

130.0 (q, JF,C = 31.5 Hz, C-CF3), 130.2 (CH), 131.5 (q, JF,C = 33.0 Hz, C-CF3), 132.3, 132.7,

133.9, 136.0, 145.2, 146.9, 154.4, 160.2 (C), 194.8 (CO). IR (KBr): v = 3078, 2999, 2962, 2918,

2849, 2837 (w), 1699 (s), 1667, 1660, 1651, 1613 (w), 1593(s), 1574 (m), 1557, 1539 (w), 1520,

1471(m), 1463, 1455, 1435, 1416, 1410, 1354 (w), 1418, 1410 (m), 1318, 1280 (s), 1264 (m),

1244, 1160 (s), 1148 (m), 1120, 1112, 1068, 1058 (s), 1033 (m), 1016 (s), 964, 937, 916, 987,

867, 856 (m), 819 (s), 799, 781 (m), 766, 756 (w), 730, 719, 709, 698, 618, 601, 554 (m) cm-1.

GC-MS (EI, 70 eV): m/z (%) = 524 ([M]+, 100). HRMS (EI, 70 eV): calcd for C30H18F6O2 [M]+:

�� !��%��)�34,�� !9'

Site-Selective Synthesis of Arylated-1-methyl-1H-indole by Suzuki–Miyaura Cross-Coupling Reactions of 2,3,6-tribromo-1-methyl-1H-indole

Synthesis of 2,3,6-tribromo-1-methyl-1H-indole (21): To a THF solution (50 mL) of N-

methylindole 20 (0.96 g, 7.34 mmol) was portion wise added NBS (4.40 g,

24.9 mmol) at -78°C and the solution was stirred at this temperature for 4

h and then at 20°C for 14 h. To the solution was added water (25 mL). The

organic and the aqueous layer were separated and the latter was extracted

with CH2Cl2 (3 x 30 mL). The combined organic layers were washed with a saturated aqueous

solution of NaHCO3, dried (Na2SO4), filtered and concentrated in vacuo. The residue was

purified by flash silica column chromatography (pure heptanes) to yield 21 as a yellowish solid

(1.85 g, 69.5%), Mp.94-96°C. 1H NMR (300 MHz, CDCl3): δ = 3.57 (s, 3H, NCH3), 7.12 (dd,

1H, J = 1.56, 8.49 Hz, ArH), 7.17-7.20 (m, 1H, ArH), 7.25 (d, 1H, J = 1.26 Hz, ArH). 13C NMR

(62.9 MHz, CDCl3): δ = 32.4 (NCH3), 92.9 (C), 112.5 (CH), 115.6, 116.6 (C), 120.0, 124.0

(CH), 125.7, 136.7 (C). IR (KBr): v = 3207, 3105, 3069, 2935, 2860, 2817, 2679 (w), 1494 (m),

1452 (s), 1410 (m), 1359 (w), 1321, 1314 (s), 1287 (m), 1226 (s), 1195, 1182, 1132 (w), 1112

(m), 1081 (w), 1048 (m), 946 (s), 847, 839 (w), 829, 790 (s), 731 (m), 666 (w), 649 (m), 597 (w),

582 (s), 562 (m) cm−1. GC-MS (EI, 70 eV): m/z (%): 369 ([(M+H), 79Br, 81Br, 81Br]+, 97), 367

([(M+H), 79Br, 79Br, 81Br]+, 100), 365 ([(M+H), 79Br, 79Br, 79Br]+ 34), 354 (18), 352 (19). HRMS

(EI, 70 eV): calcd for C9H6Br3N [M, 79Br, 81Br, 81Br]+,�� # #!!�!%� �)�34�� # #!!��, calcd for

C9H6Br3N [M, 79Br, 79Br, 81Br]+,� � #!��%� �)�34� � #!��, calcd for C9H6Br3N [M, 79Br,

79Br, 79Br]+: 364.80449; found 364.80426.

��

General procedure (A) for Suzuki cross-coupling reactions of brominated N-methylindole

(21): The reaction was carried out in a pressure tube. To a 1,4-dioxane or a mixture solvent (for

mono cross-coupling reactions) of toluene/1,4-dioxane (4:1) (3-5 mL) suspension of the

brominated -N-methylindole, Pd(PPh3)4 (3-5 mol%) and of the arylboronic acid (1.1 per cross

coupling), K3PO4 (1.5 equiv. per cross coupling) or an aqueous solution of K2CO3 (2 M, 1 mL)

was added. The mixture was heated at the indicated temperature (65-110°C) under Argon

atmosphere for the indicated period of time (8 h). The reaction mixture was diluted with water

and extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were dried (Na2SO4),

filtered and the filtrate was concentrated in vacuo. The residue was purified by flash


Synthesis of 2,3,6-triaryl-1-methyl-1H-indole 22a-i:

2,3,6-Tris(4-methoxyphenyl)-1-methyl-1H-indole (22a): Starting with 21 (100 mg, 0.27

mmol), 4-methoxyphenylboronic acid 3h (142 mg,

0.93 mmol), Pd(PPh3)4 (16 mg, 5 mol%), K2CO3 (2 M,

1 mL) and 1,4-dioxane (5 mL), 22a was isolated as a

?$�.�� 2)��4� �!9� 0:�� #9@�%� reaction temperature:

110°C for 8 h, Mp.124-126°C. 1H NMR (300 MHz,

CDCl3): δ = 3.67 (s, 3H, NCH3), 3.72 (s, 3H, OCH3),

3.75 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 6.68 (d, 1H, J = 2.94 Hz, ArH), 6.75-6.94 (m, 6H,

ArH), 7.14-7.16 (m, 3H, ArH), 7.30 (dd, 1H, J = 1.50, 8.28 Hz, ArH), 7.44 (d, 1H, J = 0.99 Hz,

ArH), 7.55 (d, 2H, J = 8.76 Hz, ArH), 7.68 (d, 1H, J = 8.25 Hz, ArH). 13C NMR (62.9 MHz,

CDCl3): δ = 30.9 (NCH3), 55.2, 55.3, 55.4 (OCH3), 107.6, 113.8, 114.2 (CH), 114.3 (C), 114.8,

116.0, 119.6 (CH), 124.2, 126.1, 127.8 (C), 128.4, 130.8, 132.3 (CH), 135.2, 137.6, 137.7, 149.5,

157.5, 158.7, 159.3 (C). IR (KBr): v = 3053, 3037, 2994, 2961, 2928, 2838, 1607, 1573, 1551

(w), 1515 (m), 1478 (w), 1466, 1455, 1440 (m), 1426, 1392, 1370, 1338, 1303 (w), 1286 (m),

1239, 1173 (s), 1148, 1107, 1089 (m), 1036, 1026 (s), 961, 944, 932, 856 (w), 838 (m), 820, 809,

795 (s), 755 (m), 729, 721 (w), 688 (m), 646, 640, 628, 625 (w), 611 (s), 586, 576 (m), 556 (w),

537 (m) cm−1. GC-MS (EI, 70 eV): m/z (%): 449 (�M]+, 100), 435 (11), 434 (36). HRMS (EI, 70

eV): calcd for C30H27O3N [M]+: ��' �'#��%��)�34,��' �''��

��

��

��

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2,3,6-Tris(4-(tert-butyl)phenyl)-1-methyl-1H-indole (22b): Starting with 21 (100 mg, 0.27

mmol), 4-tert-butylphenylboronic acid 3c (166 mg, 0.93

mmol), Pd(PPh3)4 (16 mg, 5 mol%), K2CO3 (2 M, 1

mL) and 1,4-dioxane (5 mL), 22b was isolated as a

?$�.��2)��4��0:��#�@�%�reaction temperature: 110°C

for 8 h, Mp.116-117°C. 1H NMR (300 MHz, CDCl3): δ

= 1.24 (s, 9H, 3CH3), 1.28 (s, 9H, 3CH3), 1.30 (s, 9H,

3CH3), 3.60 (s, 3H, NCH3), 6.16-7.21(m, 5H, ArH),

7.30-7.37 (m, 3H, ArH), 7.39 (d, 3H, J = 3.54 Hz, ArH), 7.49 (d, 1H, J = 1.05 Hz, ArH), 7.57

(d, 2H, J = 8.49 Hz, ArH), 7.76 (d, 1H, J = 8.04 Hz, ArH). 13C NMR (75.5 MHz, CDCl3):

δ = 31.0 (NCH3), 31.3, 31.4, 31.5 (CH3), 34.4, 34.5, 34.7 (C), 107.9 (CH), 114.7 (C), 119.8,

119.9, 125.4, 125.5, 125.7 (CH), 126.4 (C), 127.1 (CH), 128.9 (C), 129.3, 130.8 (CH), 132.2,

135.4, 137.8, 138.2, 139.7, 148.0, 149.5, 150.9 (C). IR (KBr): v = 3029 (w), 2956 (s), 2902, 2865

(m), 1911, 1673, 1604, 1548, 1519 (w), 1461 (s), 1426, 1392 (w), 1361 (s), 1335, 1318, 1307

(w), 1267 (m), 1201, 1181, 1166 (w), 1108 (m), 1086, 1047 (w), 1014, 947 (m), 921, 907 (w),

860 (m), 835, 809 (s), 769, 756 (w), 732 (m), 711, 699, 672, 651 (w), 623, 599 (m), 554 (s) cm−1.

GC-MS (EI, 70 eV): m/z (%) : 528 ([M+H]+, 38), 527 ([M]+, 100), 513 (11), 512 (26), 471 (12),

249 (9). HRMS (EI, 70 eV): calcd for C39H45N [M]+: ��9 �� %��)�34,��9 ��

2,3,6-Tris(4-ethylphenyl)-1-methyl-1H-indole (22c): Starting with 21 (100 mg, 0.27 mmol),

4-ethylphenylboronic acid 3b (140 mg, 0.93 mmol),

Pd(PPh3)4 (16 mg, 5 mol%), K2CO3 (2 M, 1 mL) and

1,4-dioxane (5 mL), 22c was isolated as a white solid

''� 0:�� #�@�%� reaction temperature: 110°C for 8 h,

Mp.116-117°C. 1H NMR (300 MHz, CDCl3): δ = 1.14-

1.24 (m, 9H, 3CH3), 2.52-2.66 (m, 6H, 3CH2), 3.60 (s,

3H, NCH3), 7.03 (d, 2H, J = 8.31 Hz, ArH), 7.14-7.23 (m, 8H, ArH), 7.34 (dd, 1H, J = 1.56,

8.28 Hz, ArH), 7.48 (d, 1H, J = 1.02 Hz, ArH), 7.55 (d, 2H, J = 8.19 Hz, ArH), 7.74 (d, 1H, J =

8.28 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 15.3, 15.4, 15.7 (CH3), 28.5, 28.6, 28.7 (CH2),

31.0 (NCH3), 107.9 (CH), 114.8 (C), 119.8, 119.9 (CH), 126.4 (C), 127.7, 127.9, 128.0, 128.2

(CH), 128.3 (C), 129.3, 130.2 (CH), 132.6, 135.6, 137.9, 138.3, 140.0, 141.2, 142.7, 144.1 (C).

IR (KBr): v = 3020, 2963, 2929, 2872 (w), 1608, 1566, 1546 (w), 1517, 1463 (m), 1428, 1409,

��

1392 (w), 1373 (m), 1341, 1317, 1256, 1229, 1182, 1147, 1118 (w), 1087 (m), 1059, 1047, 1014,

961 (w), 944 (m), 908, 855 (w), 830, 822, 806 (s), 753, 730, 700, 688, 664, 646, 640, 629 (w),

611 (m), 583, 564 (w), 535 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) : 444 ([M+H]+, 37), 443

([M]+, 100). HRMS (ESI, 70 eV): calcd for C33H34N [M+H]+: �� #�#%��)�34,�� #��

1-Methyl-2,3,6-tri-p-tolyl-1H-indole (22d): Starting with 21 (100 mg, 0.27 mmol),

4-methylphenylboronic acid 3e (126 mg, 0.93 mmol),

Pd(PPh3)4 (16 mg, 5 mol%), K2CO3 (2 M, 1 mL) and

1,4-dioxane (5 mL), 22d was isolated as a white solid

' � 0:�� #9@�%� reaction temperature: 110°C for 8 h,

Mp.174-177°C. 1H NMR (300 MHz, CDCl3): δ = 2.23

(s, 3H, CH3), 2.30 (s, 3H, CH3), 2.31 (s, 3H, CH3), 3.58

(s, 3H, NCH3), 6.99 (d, 2H, J = 7.86 Hz, ArH), 7.07-7.18 (m, 8H, ArH), 7.32 (dd, 1H, J = 1.53,

8.28 Hz, ArH), 7.46 (d, 1H, J = 1.02 Hz, ArH), 7.51 (d, 2H, J = 8.10 Hz, ArH), 7.71 (d, 1H, J =

8.31 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 21.1, 21.2, 21.4 (CH3), 31.0 (NCH3), 107.9

(CH), 114.8 (C), 119.8, 119.9 (CH), 126.4 (C), 127.3, 129.0, 129.2 (CH), 129.3 (C), 129.5,

129.7, 131.0 (CH), 132.4, 135.0, 135.6, 136.3, 137.8, 137.9, 138.3, 139.8 (C). IR (KBr): v

= 3018, 2917, 2860, 2733, 1610, 1567, 1548 (w), 1518, 1468 (m), 1449, 1428, 1403, 1391 (w),

1373 (m), 1337, 1319, 1304, 1256, 1229, 1212, 1185, 1147, 1112 (w), 1087 (m), 1039, 1015,

971, 962 (w), 944, 852 (m), 840, 820, 810, 801 (s), 777, 755, 726 (m), 698, 689, 642, 633 (w),

612 (m), 577, 567, 539 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 402 ([M+H]+, 33), 401 ([M]+,

100), 371 (6). HRMS (ESI, 70 eV): calcd for C30H28N [M+H]+: 402 �� %��)�34,��!� ��

2,3,6-Tris(4-chlorophenyl)-1-methyl-1H-indole (22e): Starting with 21 (100 mg, 0.27 mmol),

4-chlorophenylboronic acid 3f (145 mg, 0.93 mmol),

Pd(PPh3)4 (16 mg, 5 mol%), K2CO3 (2 M, 1 mL) and 1,4-

dioxane (5 mL), 22e was isolated as a white solid (108

0:��#�@�%�reaction temperature: 110°C for 8 h, Mp.218-

222°C. 1H NMR (300 MHz, CDCl3): δ = 3.60 (s, 3H,

NCH3), 7.10-7.21 (m, 6H, ArH), 7.29-7.37 (m, 5H, ArH),

7.47 (d, 1H, J = 1.02 Hz, ArH), 7.54 (d, 2H, J = 8.58 Hz, ArH), 7.68 (d, 1H, J = 8.22 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 30.0 (NCH3), 107.1 (CH), 113.4 (C), 118.8, 119.1 (CH),

��

125.2 (C), 127.5, 127.6, 127.8, 127.9 (CH), 128.8 (C), 129.9 (CH), 130.7 (C), 131.2 (CH), 131.8,

132.2, 133.5, 133.9, 136.3, 136.9, 139.6 (C). IR (KBr): v = 3078, 3031, 2923, 2852, 1899, 1614,

1598, 1568, 1543 (w), 1495 (m), 1461 (s), 1426, 1396 (w), 1370, 1334 (m), 1315, 1299 (w),

1254 (m), 1233, 1176, 1164 (w), 1088, 1013 (s), 957 (w), 946, 904 (m), 870 (w), 853 (s), 831,

821 (m), 811 (s), 760 (w), 746 (m), 732 (s), 720, 706 (m), 661, 644, 633, 625 (w), 614, 583 (m),

563, 541 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 464 ([M+H], 35Cl, 35Cl, 37Cl)+, 29), 463 ([M,35Cl, 35Cl, 37Cl]+, 99), 462 ([(M+H), 35Cl, 35Cl, 35Cl]+, 31), 461 ([M, 35Cl, 35Cl, 35Cl]+, 100).

HRMS (EI, 70 eV): calcd for C27H18Cl3N [M, 35Cl, 35Cl, 37Cl]+: 463.04698; found: 463.04719,

calcd for C27H18Cl3N [M, 35Cl, 35Cl, 35Cl]+: 461.04993; found: 461.04975.

2,3,6-Tris(3-chlorophenyl)-1-methyl-1H-indole (22f): Starting with 21 (100 mg, 0.27 mmol),

3-chlorophenylboronic acid 3n (145 mg, 0.93 mmol),


dioxane (5 mL), 22f was isolated as a white solid (101 mg,

#!@�%� reaction temperature: 110°C for 8 h, Mp.120-123°C. 1H NMR (300 MHz, CDCl3): δ = 3.63 (s, 3H, NCH3), 6.99-

7.02 (m, 1H, ArH), 7.09-7.11 (m, 3H, ArH), 7.21-7.35 (m, 7H, ArH), 7.46-7.49 (m, 2H, ArH),

7.59-7.60 (m, 1H, ArH), 7.70 (d, 1H, J = 8.13 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 30.1

(NCH3), 107.3 (CH), 113.4 (C), 118.9, 119.3, 124.5, 125.0 (CH), 125.3 (C), 125.8, 126.4, 126.9,

127.7, 128.3, 128.5, 128.6, 128.9, 129.0, 129.7 (CH), 132.1, 133.1, 133.4, 133.6, 133.8, 135.4,

136.3, 136.8, 143.0 (C). IR (KBr): v = 3066, 2917, 2849 (w), 1592 (s), 1564 (w), 1550 (m), 1485

(w), 1467 (s), 1455 (m), 1427, 1410, 1397 (w), 1373 (s), 1334 (m), 1308, 1296 (w), 1256 (m),

1165, 1140 (w), 1099, 1088, 1077 (m), 1050, 1034, 995 (w), 963 (m), 910 (w), 894, 866, 856

(m), 825, 787, 781, 771, 758, 717, 700, 688, 676 (s), 661 (w), 646 (s), 603, 583, 557, 551, 541

(w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 464 [(M+H), 35Cl, 35Cl, 37Cl]+, 29), 463 ([M, 35Cl, 35Cl,37Cl]+, 98), 462 ([(M+H), 35Cl, 35Cl, 35Cl]+, 29), 461 ([M, 35Cl, 35Cl, 35Cl]+, 100). HRMS (EI, 70

eV): calcd for C27H18Cl3N [M, 35Cl, 35Cl, 37Cl]+: 463.04698; found: 463.04738, calcd for

C27H18Cl3N [M, 35Cl, 35Cl, 35Cl]+: 461.04993; found: 461.05006.

��

2,3,6-Tris(4-fluorophenyl)-1-methyl-1H-indole (22g): Starting with 21 (100 mg, 0.27 mmol),

4-fluorophenylboronic acid 3j (130 mg, 0.93 mmol),


dioxane (5 mL), 22g was isolated as a white solid (95 mg,

#�@�%�reaction temperature: 110°C for 8 h, Mp.178-180°C. 1H NMR (300 MHz, CDCl3): δ = 3.62 (s, 3H, NCH3), 6.87-

6.93 (m, 2H, ArH), 6.98-7.10 (m, 4H, ArH), 7.12-7.24 (m,

4H, ArH), 7.30 (dd, 1H, J = 1.56, 8.28 Hz, ArH), 7.45 (d, 1H, J = 1.02 Hz, ArH), 7.53-7.59 (m,

2H, ArH), 7.67 (d, 1H, J = 8.28 Hz, ArH). 19F NMR (282.4 MHz, CDCl3): � = -116.8, -116.6, -

112.7. 13C NMR (75.5 MHz, CDCl3): δ = 29.9 (NCH3), 107.0 (CH), 113.3 (C), 114.2 (d, JF,C

= 21.2 Hz, CH), 114.6 (d, JF,C = 21.4 Hz, CH), 114.7 (d, JF,C = 21.6 Hz, CH), 118.6, 119.1 (CH),

125.2 (C), 126.5 (d, JF,C =3.54 Hz, C), 127.9 (d, JF,C = 8.00 Hz, CH), 129.7 (d, JF,C = 3.28 Hz, C),

130.2 (d, JF,C = 7.76 Hz, CH), 131.8 (d, JF,C = 8.20 Hz, CH), 134.1, 136.3, 136.7 (C), 137.4 (d,

JF,C = 3.19 Hz, C), 160.2 (d, JF,C = 245.1 Hz, C-F), 160.7 (d, JF,C = 246.1 Hz, C-F), 161.6 (d, JF,C

= 248.1 Hz, C-F). IR (KBr): v = 3068, 3043, 2961, 2853, 1907, 1891 (w), 1601, 1593, 1556 (m),

1513 (s), 1493 (m), 1463 (s), 1425, 1403 (w), 1367, 1335 (m), 1315, 1299 (w), 1258 (m), 1219,

1156, 1087, 1014 (s), 946 (m), 907 (w), 860, 837 (m), 819, 811, 800, 794 (s), 762 (w), 730 (m),

724, 686, 643, 628 (w), 608 (s), 576 (w), 566 (m), 538 (w) cm−1. GC-MS (EI, 70 eV): m/z (%):

414 ([M+H]+, 30), 413 ([M]+, 100), 397 (9). HRMS (EI, 70 eV): calcd for C27H18F3N [M]+:

413.13859; found: 413.13909.

1-Methyl-2,3,6-tris(4-(trifluoromethyl)phenyl)-1H-indole (22h): Starting with 21 (100 mg,

0.27 mmol), 4-(trifluoromethyl)phenylboronic acid 3q

(177 mg, 0.93 mmol), Pd(PPh3)4 (16 mg, 5 mol%),

K2CO3 (2 M, 1 mL) and 1,4-dioxane (5 mL), 22h was

�2)�/.�4� /2� /� ?$�.�� 2)��4� ��9� 0:�� #�@�%� reaction

temperature: 110°C for 8 h,�Mp.200-202°C. 1H NMR

(300 MHz, CDCl3): δ = 3.67 (s, 3H, NCH3), 7.30 (d,

2H, J = 1.56 Hz, ArH), 7.36-7.42 (m, 3H, ArH), 7.47 (d, 2H, J = 8.13 Hz, ArH), 7.56 (d, 1H, J

= 0.84 Hz, ArH), 7.59-7.65 (m, 4H, ArH), 7.71-7.76 (m, 3H, ArH). 19F NMR (282.4 MHz,

CDCl3): � = -62.7, -62.3, -62.3. 13C NMR (62.9 MHz, CDCl3): δ = 30.2 (NCH3), 107.7 (CH),

113.8 (C), 119.0, 119.7 (CH), 122.9 (q, JF,C = 273.3 Hz, CF3), 123.5 (q, JF,C = 272.7 Hz, CF3),

��

123.7 (q, JF,C = 272.0 Hz, CF3), 124.4 (q, JF,C = 3.74 Hz, CH), 124.6 (q, JF,C = 3.79 Hz, CH),

124.9 (q, JF,C = 3.56 Hz, CH), 125.5 (C), 126.6 (CH), 127.0 (q, JF,C = 32.4 Hz, C-CF3), 127.9 (q,

JF,C = 32.4 Hz, C-CF3), 128.8 (CH), 129.6 (q, JF,C = 32.6 Hz, C-CF3), 130.3 (CH), 133.9, 134.0,

136.6, 137.1, 137.3, 144.5 (C). IR (KBr): v = 3051, 2957, 2923, 2852, 2640 (w), 1613 (m), 1574,

1553, 1520, 1494 (w), 1465 (m), 1431, 1416, 1407, 1397, 1369 (w), 1321 (s), 1257 (m), 1187

(w), 1160 (m), 1105, 1089, 1163, 1012 (s), 960, 946 (w), 858, 841 (m), 828, 807 (s), 779, 771,

761, 742, 712 (w), 696 (m), 675, 654, 650 (w), 634, 614, 599 (m), 576 (w) cm−1. GC-MS (EI,

70 eV): m/z (%): 564 ([M+H]+, 39), 563 ([M]+, 100), 97 (10), 84 (13), 71 (18), 69 (27), 57 (28).

HRMS (EI, 70 eV): calcd for C30H18F9N [M]+: 563.12900; found: 563.12941.

1-Methyl-2,3,6-tris(3-(trifluoromethyl)phenyl)-1H-indole (22i): Starting with 21 (100 mg,

0.27 mmol), 3-(trifluoromethyl)phenylboronic acid 3g

(177 mg, 0.93 mmol), Pd(PPh3)4 (16 mg, 5 mol%), K2CO3

(2 M, 1 mL) and 1,4-dioxane (5 mL), 22i was isolated as a

?$�.�� 2)��4� ��!�0:�� 9#@�%� reaction temperature: 110°C

for 8 h,�Mp.158-160°C. 1H NMR (300 MHz, CDCl3): δ =

3.66 (s, 3H, NCH3), 7.28-7.46 (m, 8H, ArH), 7.48-7.58 (m, 4H, ArH), 7.71 (d, 1H, J = 8.34 Hz,

ArH), 7.76-7.78 (m, 1H, ArH), 7.85 (brs, 1H, ArH). 19F NMR (282.4 MHz, CDCl3): � = -62.9, -

62.8, -62.5. 13C NMR (75.5 MHz, CDCl3): δ = 30.1 (NCH3), 107.5 (CH), 113.7 (C), 118.9, 119.5

(CH), 121.6 (q, JF,C = 3.74 Hz, CH), 122.5 (q, JF,C = 3.75 Hz, CH), 122.7 (q, JF,C = 272.5 Hz,

CF3), 123.0 (q, JF,C = 272.5 Hz, CF3), 123.1 (q, JF,C = 3.79 Hz, CH), 123.3 (q, JF,C = 272.5 Hz,

CF3), 124.2 (q , JF,C = 3.67 Hz, CH), 125.4 (q, JF,C = 3.76 Hz, CH), 126.7 (q, JF,C = 3.72 Hz, CH),

127.9, 128.2, 128.3, 129.7 (CH), 129.8 (q, JF,C = 25.3 Hz, C-CF3), 130.1 (q, JF,C = 27.4 Hz, C-

CF3), 130.2 (q, JF,C = 30.7 Hz, C-CF3), 130.9 (C), 131.8, 133.3 (CH), 134.0, 134.2, 136.4, 137.1,

141.8 (C). IR (KBr): v = 3073, 3046, 2960, 2924, 2853, 1610, 1590, 1551, 1494, 1465, 1439,

1424, 1411, 1375 (w), 1334, 1326, 1308 (s), 1270 (w), 1251, 1159, 1112, 1094, 1071 (s), 1049,

1034 (m), 1000, 986, 964 (w), 912 (s), 879, 862, 829, 809 (m), 795 (s), 783 (m), 764 (w), 724

(m), 698 (s), 677 (w), 670 (s), 644, 622, 612, 595, 571, 528 (w) cm−1. GC-MS (EI, 70 eV): m/z

(%): 564 ([M+H]+, 27), 563 ([M]+, 100), 547 (15), 69 (19). HRMS (ESI, 70 eV): calcd for

C30H19F9N [M+H]+: 564.13683; found: 564.13740.

��

Synthesis of 2,6-diaryl-3-bromo-1-methyl-1H-indole 23a-e:

3-Bromo-2,6-bis(4-methoxyphenyl)-1-methyl-1H-indole (23a): Starting with 21 (100 mg, 0.27

mmol), 4-methoxyphenylboronic acid 3h (86 mg,

0.57 mmol), Pd(PPh3)4 (16 mg, 5 mol%), K3PO4

(172 mg, 0.81 mmol) and 1,4-dioxane (5 mL), 23a

?/2��2)�/.�4�/2�/�?$�.��2)��4�' �0:��#�@�%�reaction

temperature: 90°C for 8 h, Mp.163-165°C (CH2Cl2/EtOH 1:1). 1H NMR (300 MHz, CDCl3): δ =

3.58 (s, 3H, NCH3), 3.77 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 6.87-6.98 (m, 4H, ArH), 7.31-7.37

(m, 4H, ArH), 7.49-7.54 (m, 3H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 30.6 (NCH3), 54.3,

54.4 (OCH3), 88.8 (C), 106.7, 112.9, 113.2, 118.3, 119.1 (CH), 121.5, 125.2 (C), 127.4, 130.9

(CH), 133.7, 134.9, 136.2, 137.3, 157.8, 158.8 (C). IR (KBr): v = 3033, 2998, 2961, 2932, 2833

(w), 1606 (m), 1573, 1562, 1542 (w), 1518, 1489, 1461, 1443, 1424 (m), 1372 (w), 1345, 1305,

1288, 1274 (m), 1246, 1175 (s), 1105, 1035 (m), 1019 (s), 950 (m), 864 (w), 845, 832 (m), 815,

804, 781 (s), 747, 732, 704, 687, 668, 643, 629 (w), 621, 600, 576 (m), 556 (w) cm−1. GC-MS

(EI, 70 eV): m/z (%): 424 ([(M+H), 81Br]+, 25), 423 ([M, 81Br]+, 99), 422 ([(M+H), 79Br]+, 28),

421 ([M, 79Br]+, 100), 408 (34), 406 (33), 212 (13). HRMS (EI, 70 eV): calcd for C23H20BrNO2

[M, 79Br]+,�� ! 9�'%� found: 421.06734, calcd for C23H20BrNO2 [M, 81Br]+,�� ! ��%��)�34:

421.06567.

3-Bromo-2,6-bis(4-ethylphenyl)-1-methyl-1H-indole (23b): Starting with 21 (100 mg, 0.27

mmol), 4-ethylphenylboronic acid 3b (85 mg, 0.57 mmol),

Pd(PPh3)4 (16 mg, 5 mol%), K3PO4 (172 mg, 0.81 mmol)

and 1,4-dioxane (5 mL), 23b was isolated as a white solid

'!�0:��9'@�%�reaction temperature: 90°C for 8 h, Mp.119-

121°C (CH2Cl2/EtOH 1:1). 1H NMR (300 MHz, CDCl3): δ

= 1.19-1.26 (m, 6H, 2CH3), 2.59-2.70 (m, 4H, 2CH2), 3.61 (s, 3H, NCH3), 7.24 (q, 4H, J = 8.31

Hz, ArH), 7.35 (d, 2H, J = 8.25 Hz, ArH), 7.39 (dd, 1H, J = 1.47, 8.19 Hz, ArH), 7.43 (d, 1H, J

= 0.75 Hz, ArH), 7.50-7.57 (m, 3H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 15.3, 15.7 (CH3),

28.6, 28.8 (CH2), 31.7 (NCH3), 89.9 (C), 108.1, 119.5, 120.4 (CH), 126.5 (C), 127.4 (CH), 127.6

(C), 127.8, 127.9, 130.6 (CH), 136.4, 137.4, 138.7, 139.6, 143.0, 144.9 (C). IR (KBr): v = 3050,

3019, 2966, 2930, 2872, 2853, 1517, 1492 (w), 1456 (s), 1423, 1410 (w), 1370, 1342 (m), 1309,

1272, 1231 (w), 1216 (m), 1182, 1139, 1115 (w), 1101 (m), 1051, 1017, 964 (w), 949 (s), 908,

��

858 (w), 844, 835 (m), 812 (s), 771, 763 (m), 750, 732, 685, 676, 647, 631 (w), 619, 603 (m),

562 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 419 ([M, 81Br]+, 99), 418 ([(M+H), 79Br]+, 28), 417

([M, 79Br]+, 100], 404 (27), 402 (26). HRMS (EI, 70 eV): calcd for C25H24BrN [M, 81Br]+:

��' �! �%��)�34: 419.10785, calcd for C25H24BrN [M, 79Br]+: ��9 �!# %��)�34,��9.10911.

3-Bromo-1-methyl-2,6-di-p-tolyl-1H-indole (23c): Starting with 21 (100 mg, 0.27 mmol),

4-methylphenylboronic acid 3e (77 mg, 0.57 mmol),

Pd(PPh3)4 (16 mg, 5 mol%), K3PO4 (172 mg, 0.82

mmol) and 1,4-dioxane (5 mL), 23c was isolated as a

w$�.�� 2)��4� 9#� 0:�� 9�@�%� reaction temperature: 90°C

for 8 h, Mp.135-137°C. 1H NMR (300 MHz, CDCl3): δ = 2.30 (s, 3H, CH3), 2.37 (s, 3H, CH3),

3.62 (s, 3H, NCH3), 7.06-7.11 (m, 1H, ArH), 7.21-7.27 (m, 3H, ArH), 7.33(d, 2H, J = 8.24 Hz,

ArH), 7.39 (dd, 1H, J = 1.45, 8.24 Hz, ArH), 7.43 (brs, 1H, ArH), 7.49-7.57 (m, 3H, ArH). 13C

NMR (62.9 MHz, CDCl3): δ = 21.1, 21.4 (CH3), 31.7 (NCH3), 89.9 (C), 107.9, 119.4, 120.8

(CH), 120.8, 123.1, 126.4 (C), 127.3, 129.2, 129.5, 130.5 (CH), 136.3, 136.6, 137.3, 138.7, 139.3

(C). IR (KBr): v = 3022, 2916, 2852, 2729, 1908, 1613, 1556 (w), 1518, 1492 (m), 1455 (s),

1423 (w), 1368, 1341 (m), 1312, 1299, 1253, 1231 (w), 1218 (m), 1183, 1139 (w), 1105 (m),

1059, 1039, 1018, 965 (w), 950 (s), 939 (m), 907, 854 (w), 840, 821 (m), 806 (s), 779 (m), 748

(w), 721 (m), 687, 672, 649, 631 (w), 622, 598 (m), 570, 537 (w) cm−1. GC-MS (EI, 70 eV): m/z

(%) : 392 ([(M+H), 81Br]+, 24), 391 ([M, 81Br]+, 100), 390 [(M+H), 79Br]+, 31), 389 ([M, 79Br]+,

100), 295 (11), 294 (14). HRMS (EI, 70 eV): calcd for C23H20BrN [M, 81Br]+: 391.07532; found:

391.07571, calcd for C23H20BrN [M, 79Br]+: �#' !99� %��)�34, 389.07745.

3-Bromo-2,6-bis(4-chlorophenyl)-1-methyl-1H-indole (23d): Starting with 21 (100 mg, 0.27

mmol), 4-chlorophenylboronic acid 3f (89 mg, 0.57

mmol), Pd(PPh3)4 (16 mg, 5 mol%), K3PO4 (172 mg,

0.81 mmol) and 1,4-dioxane (5 mL), 23d was isolated as

/�?$�.�� 2)��4� '��0:��#!@�%� reaction temperature: 90°C

for 8 h, Mp.173-175°C. 1H NMR (300 MHz, CDCl3): δ = 3.61 (s, 3H, NCH3), 7.31-7.44 (m, 8H,

ArH), 7.49-7.58 (m, 3H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 30.7 (NCH3), 88.5 (C), 107.1,

118.8, 119.4 (CH), 125.8 (C), 127.6, 127.8, 127.9, 130.9 (CH), 131.2, 132.0, 134.0, 134.4, 136.4,

136.5, 139.4 (C) . IR (KBr): v = 3069, 3054, 3013, 2961, 2924, 2872, 2851, 1598, 1557, 1542,

1498 (w), 1478, 1463 (m), 1426, 1399, 1367, 1340, 1306, 1296 (w), 1258 (m), 1236, 1213, 1180,

��

1124 (w), 1104 (m), 1089 (s), 1056 (m), 1009 (s), 950, 939 (m), 907, 861 (w), 838 (s), 823, 813

(m), 797 (s), 742, 733 (w), 725 (m), 715, 698, 673, 666, 648, 639, 626 (w), 609 (m), 592, 582,

538 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 431 ([(M+H), 81Br, 35Cl]+, 100), 430 ([M, 81Br,35Cl]+, 15), 429 ([(M+H), 79Br, 35Cl]+, 63), 393 (8), 314 (10), 139 (16). HRMS (EI, 70 eV): calcd

for C21H14BrCl2N [M, 81Br, 35Cl]+: 430.96607; found: 430.96755, calcd for C21H14BrCl2N [M,79Br, 35Cl]+: 428.96812; found: 428.96935.

3-Bromo-2,6-bis(4-fluorophenyl)-1-methyl-1H-indole (23e): Starting with 21 (100 mg, 0.27

mmol), 4-fluorophenylboronic acid 3j (79 mg, 0.57 mmol),

Pd(PPh3)4 (16 mg, 5 mol%), K3PO4 (172 mg, 0.81 mmol)

and 1,4-dioxane (5 mL), 23e was isolated as a white solid

'!�0:��#�@�%�reaction temperature: 90°C for 8 h,�Mp.115-

117°C. 1H NMR (300 MHz, CDCl3): δ = 3.60 (s, 3H, NCH3), 7.06 (t, 2H, J = 5.22 Hz, ArH),

7.14 (t, 2H, J = 5.22 Hz, ArH), 7.35 (dd, 1H, J = 0.87, 4.92 Hz, ArH), 7.39-7.42 (m, 3H, ArH),

7.53-7.57 (m, 3H, ArH). 19F NMR (282.4 MHz, CDCl3): � = -116.3, -111.9. 13C NMR

(62.9 MHz, CDCl3): δ = 31.7 (NCH3), 90.3 (C), 108.2 (CH), 115.5 (d, JF,C = 6.51 Hz, CH), 117.3

(d, JF,C = 6.83 Hz, CH), 119.7, 120.5 (CH), 126.2, 126.3 (C), 128.9 (d, JF,C = 7.92 Hz, CH), 132.5

(d, JF,C = 8.32 Hz, CH), 135.7, 137.3, 137.7, 138.1 (C), 162.3 (d, JF,C = 245.9 Hz, C-F), 162.9 (d,

JF,C = 249.2 Hz, C-F). IR (KBr): v = 2925, 2852 (w), 1603, 1591 (m), 1574, 1557 (w), 1539 (m),

1515, 1488 (s), 1456 (m), 1424, 1405, 1371, 1339, 1308, 1298 (w), 1229, 1158, 1100 (s), 1022

(w), 1010, 951 (m), 860 (w), 846, 834, 824 (w), 794 (s), 726, 718, 686, 667, 644, 629 (w), 619

(m), 599 (s), 566 (m), 536 (w) cm−1. GC-MS (EI, 70 eV): m/z (%): 399 ([M, 81Br]+, 100), 398

([(M+H), 79Br]+, 25), 397 ([M, 79Br]+, 99), 317 (11), 316 (15), 303 (14). HRMS (EI, 70 eV):

calcd for C21H14F2BrN [M, 81Br]+: 399.02517; found: 399.02549, calcd for C21H14F2BrN [M, 79Br]+: 397.02722 found: 397.02732.

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Synthesis of 3,6-dibromo-2-aryl-1-methyl-1H-indole 24a-e:

3,6-Dibromo-2-(4-(tert-butyl)phenyl)-1-methyl-1H-indole (24a): Starting with 21 (100 mg,

0.27 mmol), 4-tert-butylphenylboronic acid 3c (52 mg, 0.29

mmol), Pd(PPh3)4 (10 mg, 3 mol%), K3PO4 (86 mg, 0.40 mmol)

and toluene/1,4-dioxane (4:1) (5 mL), 24a was isolated as a

?$�.�� 2)��4� '9�0:�� #�@�%� reaction temperature: 65°C for 8 h,

Mp.156-158°C. 1H NMR (300 MHz, CDCl3): δ = 1.31 (s, 9H, 3CH3), 3.55 (s, 3H, NCH3), 7.23

(dd, 1H, J = 1.92, 10.11 Hz, ArH), 7.31-7.46 (m, 6H, ArH). 13C NMR (62.9 MHz, CDCl3):

δ = 31.3 (CH3), 31.8 (NCH3), 33.2, 90.0 (C), 112.7 (CH), 116.2 (C), 120.5, 123.7, 125.5 (CH),

126.2, 126.8 (C), 130.2 (CH), 137.5, 138.8, 151.9 (C). IR (KBr): v = 3026 (w), 2959 (m), 2901,

2865, 2707, 1920, 1868, 1731, 1681, 1599, 1563, 1556 (w), 1491, 1461, 1451, 1416 (m), 1405,

1390 (w), 1360 (m), 1336 (s), 1289, 1267 (w), 1217 (m), 1199, 1131 (w), 1109, 1053, 1014 (m),

968 (w), 945, 842, 800 (s), 738, 723, 689 (w), 654 (m), 628 (w), 615 (s), 589 (m), 576, 553, 543

(w) cm−1.GC-MS (EI, 70 eV): m/z (%): 421 ([(M+H), 79Br, 81Br]+, 100), 420 ([M, 79Br, 81Br]+,

11), 419 (52), 408 (23), 406 (45), 404 (23), 378 (8). HRMS (EI, 70 eV): calcd for C19H19Br2N

[M, 79Br, 81Br]+: 420.98583; found: 420.98605.

3,6-Dibromo-2-(4-ethylphenyl)-1-methyl-1H-indole (24b): Starting with 21 (100 mg, 0.27

mmol), 4-ethylphenylboronic acid 24c (44 mg, 0.29 mmol),


toluene/1,4-dioxane (4:1) (5 mL), 24b was isolated as a white

2)��4� ##�0:�� #�@�%� reaction temperature: 65°C for 8 h, Mp.94-

96°C. 1H NMR (300 MHz, CDCl3): δ = 1.24 (t, 3H, CH3), 2.67 (q, 2H, J = 7.59, CH2), 3.56 (s,

3H, NCH3), 7.20-7.26 (m, 2H, ArH), 7.29 (d, 3H, J = 8.40 Hz, ArH), 7.33-7.39(m, 1H, ArH),

7.42 (d, 1H, J = 1.41 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 15.3 (CH3), 28.7 (CH2), 31.7

(NCH3), 90.1 (C), 112.7 (CH), 116.2 (C), 120.5, 123.7 (CH), 126.2, 127.1 (C), 128.0, 130.5

(CH), 137.5, 138.8, 145.1 (C). IR (KBr): v = 3070, 3022, 2960, 2868 (w), 1492, 1463, 1448 (m),

1414, 1371 (w), 1338 (m), 1305, 1289, 1231 (w), 1214 (m), 1183, 1130, 1117 (w), 1109, 1054

(m), 1040, 1015, 966 (w), 943, 934, 843, 837, 829 (s), 811 (w), 800 (s), 765, 734, 677 (w), 659

(m), 632 (w), 617 (m), 587 (s), 560 (w) cm−1. GC-MS (EI, 70 eV): m/z (%): 395 ([(M+H), 81Br]+, 49), 394 ([M, 81Br]+, 19), 393 ([(M-H), 81Br]+, 100), 392 ([M, 81Br]+, 11), 391 ([(M+H),

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79Br]+, 51), 378 (32), 376 (16). HRMS (EI, 70 eV): calcd for C17H15Br2N [M, 81Br]+: 394.95248;

found: 394.95330, calcd for C17H15Br2N [M, 79Br]+: 390.95658; found: 390.95765.

3,6-Dibromo-1-methyl-2-(p-tolyl)-1H-indole (24c): Starting with 21 (100 mg, 0.27 mmol),

4-methylphenylboronic acid 3e (40 mg, 0.29 mmol), Pd(PPh3)4

(10 mg, 3 mol%), K3PO4 (86 mg, 0.40 mmol) and toluene/1,4-

dioxane (4:1) (5 mL), 24c was isolated as a white solid (79 mg,

77%), reaction temperature: 65°C for 8 h. 1H NMR (300 MHz,

CDCl3): δ = 2.37 (s, 3H, CH3), 3.54 (s, 3H, NCH3), 7.21-7.32 (m, 5H, ArH), 7.35-7.39 (m, 1H,

ArH), 7.42 (d, 1H, J = 1.77 Hz, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 21.4 (CH3), 31.7

(NCH3), 90.1 (C), 112.7 (CH), 116.2 (C), 120.5, 123.7 (CH), 126.2, 126.9 (C), 129.3, 130.4

(CH), 137.5, 138.8, 139.0 (C). IR (KBr): v = 3206, 3070, 3021 (w), 2918 (m), 2866, 2584, 2550,

2417, 2357, 2326, 2142, 1965, 1910, 1869, 1801, 1732, 1673, 1604, 1562 (w), 1492 (m), 1462,

1450 (s), 1419, 1370 (m), 1336 (s), 1289, 1217, 1182 (m), 1131 (w), 1110, 1054 (m), 1040 (w),

1018 (m), 964 (w), 943 (s), 830, 797 (s), 781 (m), 759, 736 (w), 720 (m), 677, 658, 633 (w), 620,

586 (s), 549 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 381 ([(M+H), 81Br]+, 49), 380 ([M, 81Br]+,

19), 379 ([(M+H), 79Br, 81Br]+, 100), 377 ([(M+H), 79Br]+, 50), 218 (11), 204 (13). HRMS (EI,

70 eV): calcd for C16H13Br2N [M, 81Br]+: 380.93683; found: 380.93821, calcd for C16H13Br2N

[M, 79Br, 81Br]+: 378.93888; found: 378.93905, calcd for C16H13Br2N [M, 79Br]+: 376.94093;

found: 376.94069.

3,6-Dibromo-2-(4-chlorophenyl)-1-methyl-1H-indole (24d): Starting with 21 (100 mg, 0.27

mmol), 4-chlorophenylboronic acid 3f (46 mg, 0.29 mmol),


toluene/1,4-dioxane (4:1) (5 mL), 24d was isolated as a white

solid (86 mg, 79%), reaction temperature: 65°C for 8 h. 1H NMR

(300 MHz, CDCl3): δ = 3.54 (s, 3H, NCH3), 7.23-7.26 (m, 1H, ArH), 7.32-7.36 (m, 3H, ArH),

7.39-7.44 (m, 3H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 31.8 (NCH3), 90.7 (C), 112.8 (CH),

116.7 (C), 120.8, 124.0 (CH), 126.1, 128.4 (C), 128.9, 131.9 (CH), 135.2, 137.4, 137.6 (C). IR

(KBr): v = 3079, 3064, 2925, 2854, 1915, 1872, 1728, 1692, 1599, 1562, 1536, 1503, 1478 (w),

1461, 1454 (m), 1418, 1400, 1361 (w), 1336 (m), 1288, 1268, 1232, 1212, 1179, 1129, 1104 (w),

1088 (m), 1051, 1036 (w), 1011 (m), 966 (w), 944, 939 (m), 835 (s), 803 (m), 795 (s), 737 (w),

724 (m), 674, 648, 625 (w), 607 (m), 589 (s), 570 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 399

([(M+H), 79Br, 81Br, 35Cl]+, 100), 398 ([M, 79Br, 81Br, 35Cl]+, 8), 397 ([(M+H), 79Br, 79Br, 35Cl]+,

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45), 204 (11). HRMS (EI, 70 eV): calcd for C15H10Br2ClN [M, 79Br, 81Br, 35Cl]+: 398.88426;

found: 398.88410, calcd for C15H10Br2ClN [M, 79Br, 79Br, 35Cl]+: 396.88630; found: 396.88615.

General procedure (B) for Suzuki cross-coupling Reactions of brominated N-methylindole

(21): The reaction was carried out in a pressure tube. To a mixture solvent of toluene/dioxane

(4:1) (5 mL) suspension of the brominated -N-methylindole, Pd(PPh3)4 (5 mol%) and of the

Ar1B(OH)2 (1.1 equiv.), K3PO4 (1.5 equiv.) was added also. The mixture was heated at the

indicated temperature (65°C) under Argon atmosphere for the indicated period of time (8 h) and

cooled to room temperature. Then Ar2B(OH)2 (2.1 equiv.), K2CO3 (2 M, 1 mL) and 1,4-dioxane

(3 mL) was added. The reaction mixture was further heated for 8 h at 110°C. The reaction

mixture was again cooled to room temperature and diluted with water and extracted with CH2Cl2(3 x 25 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate was

concentrated in vacuo. The residue was purified by flash chromatography (silica gel, EtOAc/

heptanes).

Synthesis of unsymmetrical 2,3,6-triaryl-1-methyl-1H-indoles 25a-d:

3,6-Bis(4-(tert-butyl)phenyl)-2-(4-fluorophenyl)-1-methyl-1H-indole (25a): Starting with 21

(100 mg, 0.27 mmol), 4-flourophenylboronic acid 3j (41

mg, 0.29 mmol), Pd(PPh3)4 (16 mg, 5 mol%), K3PO4 (86

mg, 0.40 mmol) and toluene/ 1,4-dioxane (4:1) (5 mL), 4-

tert-butylphenylboronic acid 3c (99 mg, 0.57 mmol),

K2CO3 (2 M, 1 mL) and 1,4-dioxane (3 mL), following the

general procedure B, 25a was isolated as a yellowish solid

''� 0:�� 9�@�%� reaction temperature: at 65°C for 8 h, at

110°C for 8 h, Mp.148-150°C. 1H NMR (300 MHz, CDCl3): δ = 1.22(s, 9H, 3CH3), 1.29 (s, 9H,

3CH3), 3.56 (s, 3H, NCH3), 6.97 (t, 2H, J = 8.64 Hz, ArH), 7.10-7.25 (m, 6H, ArH), 7.34 (dd,

1H, J = 1.35, 8.31 Hz, ArH), 7.40 (d, 2H, J = 8.34 Hz, ArH), 7.47 (d, 1H, J = 0.90 Hz, ArH),

7.56 (d, 2H, J = 8.31 Hz, ArH), 7.75 (d, 1H, J = 8.31 Hz, ArH). 19F NMR (282.4 MHz, CDCl3):

� = -113.2. 13C NMR (62.9 MHz, CDCl3): δ = 30.9 (NCH3), 31.4, 31.5 (CH3), 34.4, 34.5 (C),

107.9 (CH), 115.2 (C), 115.6 (d, JF,C = 21.5 Hz, CH), 120.1, 125.2, 125.7 (CH), 126.3 (C), 127.1

(CH), 128.1 (d, JF,C = 3.49 Hz, CH), 129.3 (CH), 131.9 (C), 132.4 (d, JF,C = 8.15 Hz, CH), 135.8,

136.9, 137.9, 139.6, 148.4, 149.7 (C), 162.6 (d, JF,C = 247.9 Hz, C-F). IR (KBr): v = 3030 (w),

2957 (m), 2902, 2865, 2244, 1900, 1605, 1593, 1563, 1549 (w), 1516 (m), 1491 (w), 1462 (s),

� ��

1426, 1404, 1392 (w), 1363 (m), 1334, 1319, 1307, 1296 (w), 1267 (m), 1221 (s), 1202 (w),

1156 (m), 1108, 1093, 1086, 1045, 1014 (w), 947 (m), 906 (s), 860 (m), 836, 823, 810, 802 (s),

761, 750 (w), 729 (s), 694, 672, 649 (w), 624, 604 (m), 561 (s), 538 (w) cm−1. GC-MS (EI,

70 eV): m/z (%): 490 ([M+H]+, 61), 489 ([M]+, 100), 474 (38), 444 (8), 229 (23), 215 (36), 201

(96), 189 (16), 183 (15), 134 (14). HRMS (EI, 70 eV): calcd for C35H36FN [M]+: 489.28263;

found: 489.28253.

2-(4-(Tert-butyl)phenyl)-3,6-bis(4-methoxyphenyl)-1-methyl-1H-indole (25b): Starting with

24a (71 mg, 0.17 mmol), 4-methoxyphenylboronic

acid 3h (53 mg, 0.35 mmol), Pd(PPh3)4 (10 mg, 5

mol%), K2CO3 (2 M, 1 mL) and 1,4-dioxane (3 mL),

following the general procedure A, 25b was isolated as

a ye��)?�2$�2)��4� ��0:��#�@�%�reaction temperature:

at 90°C for 8 h, Mp.184-186°C. 1H NMR (300 MHz,

CDCl3): δ = 1.27 (s, 9H, 3CH3), 3.62 (s, 3H, NCH3), 3.72 (s, 3H, OCH3), 3.78 (s, 3H, OCH3),

6.76 (d, 2H, J = 8.76 Hz, ArH), 6.92 (d, 2H, J = 8.73 Hz, ArH), 7.16-7.18 (m, 4H, ArH), 7.31

(d, 3H, J = 8.28 Hz, ArH), 7.44 (d, 1H, J = 0.84 Hz, ArH), 7.56 (d, 2H, J = 8.70 Hz, ArH), 7.68

(d, 1H, J = 8.22 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 31.0 (NCH3), 31.3 (CH3), 34.7

(C), 55.2, 55.4 (OCH3), 107.6, 113.7, 114.2 (CH), 114.5 (C), 119.7, 125.3 (CH), 122.1, 127.8

(C), 127.4, 128.7 (CH), 128.9 (C), 130.7, 130.9 (CH), 135.3, 137.8, 138.0, 150.9, 157.6, 158.7

(C). IR (KBr): v = 3033, 2996, 2953, 2902, 2866, 2832, 2248, 2059, 1886, 1714, 1650 (w), 1607

(m), 1573, 1548 (w), 1514 (s), 1492 (w), 1461 (s), 1440 (m), 1426, 1407, 1393 (w), 1363 (m),

1334, 1316, 1302 (w), 1278 (m), 1240, 1174 (s), 1108, 1089 (w), 1035 (s), 946, 906, 858 (m),

832, 807, 794 (s), 783, 760 (w), 727 (s), 688 (m), 648, 624 (w), 607 (s), 582, 558 (w), 531 (m)

cm−1. GC-MS (EI, 70 eV): m/z (%): 476 ([M+H]+, 36), 475 ([M]+, 100), 460 (12). HRMS (ESI,

70 eV): calcd for C33H33NO2 [M+H]+: 476.25841; found: 476.25779.

2-(4-Chlorophenyl)-3,6-bis(4-methoxyphenyl)-1-methyl-1H-indole (25c): Starting with 24d

(67 mg, 0.17 mmol), 4-methoxyphenylboronic acid 3h

(54 mg, 0.35 mmol), Pd(PPh3)4 (10 mg, 5 mol%),

K2CO3 (2 M, 1 mL) and 1,4-dioxane (3 mL), following

the general procedure A, 25c was isolated as a yellowish

2)��4� ��0:��#�@�%�reaction temperature: at 90°C for 8

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h, Mp.105-107°C. 1H NMR (300 MHz, CDCl3): δ = 3.60 (s, 3H, NCH3), 3.72 (s, 3H, OCH3),

3.78 (s, 3H, OCH3), 6.77 (d, 2H, J = 8.79 Hz, ArH), 6.92 (d, 2H, J = 8.79 Hz, ArH), 7.12-7.19

(m, 4H, ArH), 7.26-7.35 (m, 3H, ArH), 7.44 (brs, 1H, ArH), 7.55 (d, 2H, J = 8.67 Hz, ArH),

7.67 (d, 1H, J = 8.36 Hz, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 30.0 (NCH3), 54.2, 54.4

(OCH3), 106.6, 112.8, 113.2, 118.8 (CH), 125.1, 126.1 (C), 127.4, 127.7 (CH), 127.8, 129.4 (C),

129.8, 131.3 (CH), 133.0, 134.0, 134.7, 135.3, 137.0, 156.8, 157.8 (C). IR (KBr): v = 3033,

2999, 2958, 2920, 2836 (w), 1606 (m), 1572, 1546 (w), 1510, 1462 (s), 1441 (m), 1426, 1395

(w), 1368 (m), 1333, 1316, 1302 (w), 1279 (m), 1242, 1174, 1087, 1033, 1013 (s), 945 (m), 907,

887, 873 (w), 856, 826 (m), 815, 804, 794 (s), 760 (w), 725 (m), 698, 684, 649, 637, 618 (w),

603 (s), 578, 568 (w), 534 (m) cm−1. GC-MS (EI, 70 eV): m/z (%) : 454 ([M+H]+, 27), 453

([M]+, 100), 438 (25). HRMS (EI, 70 eV): calcd for C29H24ClO2N [M]+: 453.14901; found:

453.14838.

2-(4-(Tert-butyl)phenyl)-3,6-bis(2-methoxyphenyl)-1-methyl-1H-indole (25d): Starting with

24a (71 mg, 0.17 mmol), 2-methoxyphenylboronic acid 3a

(54 mg, 0.36 mmol), Pd(PPh3)4 (10 mg, 5 mol%), K2CO3 (2

M, 1 mL) and 1,4-dioxane (3 mL), following the general

procedure A, 25d was isolated as a yellowish solid (58 mg,

9�@�%�reaction temperature: at 90°C for 8 h, Mp.175-177°C.1H NMR (300 MHz, CDCl3): δ = 1.24 (s, 9H, 3CH3), 3.38 (s, 3H, NCH3), 3.67 (s, 3H, OCH3),

3.74 (s, 3H, OCH3), 6.77-6.86 (m, 2H, ArH), 6.92-7.00 (m, 2H, ArH), 7.12-7.17 (m, 3H, ArH),

7.19-7.28 (m, 5H, ArH), 7.33-7.36 (m, 1H, ArH), 7.43-7.46 (m, 2H, ArH). 13C NMR (75.5 MHz,

CDCl3): δ = 30.2 (NCH3), 30.3 (CH3), 33.6 (C), 53.8, 54.7 (OCH3), 109.5, 109.9 (CH), 110.1

(C), 110.4 (CH), 118.3, 119.3, 119.8, 120.9 (CH), 123.4 (C), 123.9 (CH), 125.8 (C), 126.4, 126.9

(CH), 128.7 (C), 129.0, 130.0 (CH), 131.2, 131.4 (C), 131.7 (CH), 136.3, 138.0, 149.3, 155.7,

156.2 (C). IR (KBr): v = 3050 (w), 2954, 2924 (m), 2854, 1716, 1699, 1683, 1669, 1652, 1635,

1615, 1597, 1578, 1558, 1501 (w), 1457 (s), 1432 (m), 1406, 1394 (w), 1363 (m), 1333, 1313,

1289 (w), 1252, 1239 (s), 1178, 1160 (w), 1117, 1083, 1050 (m), 1025 (s), 947 (m), 932, 856,

838 (w), 825, 813, 792 (m), 749 (s), 699, 654 (m), 638 (w), 628 (m), 611, 592, 560, 544 (w)

cm−1. GC-MS (EI, 70 eV): m/z (%) : 476 ([M+H]+, 36), 475 ([M]+, 100). HRMS (EI, 70 eV):

calcd for C33H33NO2 [M]+: 475.25058; found: 475.25047.

��

Synthesis of Functionalized Anthraquinones by Domino Twofold Heck–6ππππ-Electrocyclization Reactions of 2,3-Dibromonaphthoquinone

General procedure for the synthesis of mono- and disubstituted anthraquinones:

In a pressure tube (glass bomb) a suspension of Pd(OAc)2 (11 mg, 5 mol%) and XPhos (48

mg, 10 mol%) in DMF (5 mL) was purged with argon and stirred at 20°C to give a yellowish or

brownish clear solution. To the stirred solution were added 26 (316 mg, 1.0 mmol), NEt3 (1.1

mL, 8.0 mmol) and the alkene 27a-j (2.5 equiv.). The reaction mixture was stirred at 90°C

(Method 1) or 110°C (Method 2) for 8 h. The solution was cooled to 20°C, poured into H2O and

CH2Cl2 (25 mL each), and the organic and the aqueous layer were separated. The latter was

extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were washed with H2O (3 x 20

mL), dried (Na2SO4), concentrated in vacuo and the residue was purified by chromatography

(flash silica gel, heptanes/ EtOAc) to give 28 or 29.

2,3-Bis(4-chlorophenyl)anthracene-9,10-dione (28a): Starting with 26 (316 mg, 1.0 mmol), 4-

chlorostyrene 27a (346 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5

mol%), XPhos (48 mg, 10 mol%), 28a was isolated as a yellowish

solid (325 mg, 76%), reaction temperature: at 90°C for 8 h, Mp.

221-223°C. 1H NMR (300 MHz, CDCl3): δ = 7.05 (d, 4H, J =

7.05 Hz, ArH), 7.20 (d, 4H, J = 8.52 Hz, ArH), 7.72-7.77 (m, 2H,

ArH), 8.21 (s, 2H, ArH), 8.23-8.26 (m, 2H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 126.3,

127.7, 128.5, 129.9 (2CH), 131.5, 132.5, 133.1 (2C), 133.2 (2CH), 136.7, 143.9 (2C), 181.6

(2CO). IR (KBr): v = 3316, 3073, 3054, 3028, 2961, 2924, 2851 (w), 1671, 1661, 1586 (s), 1565

(m), 1519, 1500 (w), 1490, 1477 (m), 1455, 1413, 1387 (w), 1329 (s), 1302, 1284 (m), 1258 (s),

1180, 1170, 1126 (w), 1087 (s), 1044 (w), 1011 (s), 969, 957 (w), 945 (s), 905 (w), 825, 796 (s),

762 (w), 748, 739, 728 (m), 712 (s), 688, 665, 644, 635, 586 (w), 560 (m), 534 (w) cm−1. GC-MS

(EI, 70 eV): m/z (%) : 431 ([(M+H), 35Cl, 37Cl]+, 17), 430 ([M, 35Cl, 37Cl]+, 69), 429

([(M+H),35Cl, 35Cl]+, 30), 428 ([M, 35Cl, 35Cl]+, 100), 393 (59), 358 (21), 330 (11), 300 (31), 150

(25). HRMS (EI, 70 eV): calcd for C26H14Cl2O2 [M, 35Cl, 37Cl]+: 430.03359; found: 430.03367,

calcd for C26H14Cl2O2 [M, 35Cl, 35Cl]+: 428.03654; found: 428.03595.

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2,3-Bis(3-chlorophenyl)anthracene-9,10-dione (28b): Starting with 26 (316 mg, 1.0 mmol), 3-

chlorostyrene 27b (346 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5

mol%), XPhos (48 mg, 10 mol%), 28b was isolated as a

yellowish solid (303 mg, 71%), reaction temperature: at 90°C for

8 h, Mp.150-152°C. 1H NMR (300 MHz, CDCl3): δ = 6.93 (d,

2H, J = 7.85 Hz, ArH), 7.10-7.22 (m, 5H, ArH), 7.35-7.53 (m, 1H, ArH), 7.72-7.78 (m, 2H,

ArH), 8.23 (s, 2H, ArH), 8.24 (m, 2H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 126.3, 126.8,

127.1, 128.4, 128.5, 128.6 (2CH), 131.6, 132.5 (2C), 133.3 (2CH), 133.4, 139.9, 143.8 (2C),

181.6 (2CO). IR (KBr): v = 3321, 3055, 3014, 2957, 2919, 2851, 1953, 1875, 1770, 1698 (w),

1670, 1584 (s), 1564 (m), 1477, 1469, 1463, 1418, 1395 (w), 1327, 1316 (s), 1286 (m), 1266,

1248 (s), 1167, 1129, 1097, 1078, 1052, 998, 977 (w), 952 (m), 928, 900, 884, 857 (w), 792, 784

(m), 755, 738 (w), 711, 702, 688 (s), 666 (m), 641, 621, 684, 656, 532 (w) cm−1. GC-MS (EI,

70 eV): m/z (%) : 431 ([(M+H), 35Cl, 37Cl]+, 19), 430 ([M, 35Cl, 37Cl]+, 66), 429 ([(M+H), 35Cl, 35Cl]+, 30), 428 ([M, 35Cl, 35Cl]+, 100), 393 (84), 358 (24), 330 (12), 300 (36), 150 (32). HRMS

(EI, 70 eV): calcd for C26H14Cl2O2 [M, 35Cl, 37Cl]+: 430.03359; found: 430.03421, calcd for

C26H14Cl2O2 [M, 35Cl, 35Cl]+: 428.03654; found: 428.03696.

2,3-Bis(4-(tert-butyl)phenyl)anthracene-9,10-dione (28c): Starting with 26 (316 mg, 1.0

mmol), 4-tert-butylstyrene 27c (400 mg, 2.5 mmol), Pd(OAc)2

(11 mg, 5 mol%), XPhos (48 mg, 10 mol%), 28c was isolated as a

yellowish solid (377 mg, 80%), reaction temperature: at 90°C for

8 h, Mp.166-168°C. 1H NMR (300 MHz, CDCl3): δ = 1.24 (s,

9H, 3CH3), 1.24 (s, 9H, 3CH3), 7.08 (d, 4H, J = 8.61 Hz, ArH),

7.21 (d, 4H, J = 8.58 Hz, ArH), 7.71-7.76 (m, 2H, ArH), 8.24-8.27 (m, 2H, ArH), 8.29 (s, 2H,

ArH). 13C NMR (62.9 MHz, CDCl3): δ = 31.3 (2CH3), 34.5 (2C), 125.0, 127.2, 129.3, 129.6

(2CH), 132.0, 133.8 (2C), 134.0 (2CH), 136.8, 146.4, 150.7 (2C), 183.1 (2CO). IR (KBr): v

= 3325, 3063, 3033, 2959, 2923, 2853, 1737 (w), 1672 (s), 1610 (w), 1587 (s), 1513, 1493, 1475,

1462, 1414, 1390, 1361 (w), 1329 (s), 1310, 1290 (m), 1259 (s), 1201, 1186, 1168 (w), 1109,

1080 (m), 1022 (w), 1013 (m), 971, 960 (w), 946 (m), 929, 896, 851 (w), 832, 800, 791 (m), 752,

734 (w), 713 (s), 690, 666, 647 (w), 588 (m), 561, 529 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) :

473 ([M+H]+, 21), 472 ([M]+, 69), 457 ([M]+, 100), 359 (13), 221 (16), 193 (23). HRMS (EI, 70

eV): calcd for C34H32O2 [M]+: 472.23968; found: 472.24008.

��

2,3-Di-p-tolylanthracene-9,10-dione (28d): Starting with 26 (316 mg, 1.0 mmol), 4-

methylstyrene 27d (295 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5

mol%), XPhos (48 mg, 10 mol%), 28d was isolated as a

yellowish solid (302 mg, 78%), reaction temperature: at 90°C

for 8 h, Mp.140-142°C. 1H NMR (250 MHz, CDCl3): δ =

2.24 (s, 3H, CH3), 2.24 (s, 3H, CH3), 6.97-6.99 (m, 7H, ArH),

7.66-7.69 (m, 2H, ArH), 8.18-8.22 (m, 5H, ArH). 13C NMR (62.9 MHz, CDCl3): δ = 21.2

(2CH3), 127.2, 128.9, 129.5, 129.6 (2CH), 132.0, 133.7 (2C), 134.0 (2CH), 136.8, 137.4, 146.3

(2C), 182.9 (2CO). IR (KBr): v = 3324, 3015, 2914, 2857 (w), 1671 (m), 1609 (w), 1586 (m),

1513, 1478, 1453, 1391 (w), 1327 (s), 1309, 1287, 1271, 1255 (m), 1208, 1184, 1169 (w), 1127,

1113 (m), 1039 (w), 1017 (m), 971 (w), 946 (m), 923, 906, 863, 850, 841 (w), 820 (s), 794 (m),

758 (w), 727 (m), 710 (s), 670, 665, 642, 636, 605, 589, 565 (w), 547 (m) cm−1.GC-MS (EI,

70 eV): m/z (%) : 389 ([M+H]+, 31), 388 ([M]+, 100), 373 (67), 187 (14). HRMS (EI, 70 eV):

calcd for C28H20O2 [M]+: 388.14578; found: 388.14581.

2,3-Bis(4-fluorophenyl)anthracene-9,10-dione (28e): Starting with 26 (316 mg, 1.0 mmol), 4-

fluorostyrene 27e (305 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5

mol%), XPhos (48 mg, 10 mol%), 28e was isolated as a yellowish

solid (285 mg, 72%), reaction temperature: at 90°C for 8 h,

Mp.164-166°C. 1H NMR (300 MHz, CDCl3): δ = 6.90 (t, 4H, J =

8.70 Hz, ArH), 7.05-7.11 (m, 4H, ArH), 7.69-7.76 (m, 2H, ArH), 8.21 (s, 2H, ArH), 8.23-8.26

(m, 2H, ArH).19F NMR (282.4 MHz, CDCl3): � = -113.7, -112.8. 13C NMR (75.5 MHz, CDCl3):

δ = 115.5 (d, JF,C = 21.6 Hz, 2CH), 127.3, 129.5 (2CH), 131.3 (d, JF,C = 8.21 Hz, 2CH), 132.4,

133.6 (2C), 134.2 (2CH), 135.4 (d, JF,C = 3.37 Hz, 2C), 145.3 (2C), 162.4 (d, JF,C = 248.6 Hz,

2C-F), 182.8 (2CO). IR (KBr): v = 3319, 3182, 3058, 2923, 2853 (w), 1670 (s), 1600 (m), 1583,

1509 (s), 1477 (m), 1434, 1392 (w), 1327 (s), 1301, 1273, 1256 (m), 1221, 1157 (s), 1128, 1097

(m), 1044 (w), 1014 (m), 976 (w), 949, 924 (m), 864 (w), 834 (s), 816, 803, 792 (m), 760 (w),

730 (m), 710 (s), 666 (m), 638, 606, 588, 581, 565 (w), 546 (m) cm−1. GC-MS (EI, 70 eV): m/z

(%) : 397 ([M+H]+, 29), 396 ([M]+, 100), 338 (22), 318 (8). HRMS (EI, 70 eV): calcd for

C26H14F2O2 [M]+: 396.09564; found: 396.09500.

��

Diethyl 9,10-dioxo-9,10-dihydroanthracene-2,3-dicarboxylate (28g): Starting with 26 (316

mg, 1.0 mmol), ethylacrylate 27g (250 mg, 2.5 mmol), Pd(OAc)2 (11

mg, 5 mol%), XPhos (48 mg, 10 mol%), 28g was isolated as a

yellowish solid (278 mg, 79%), reaction temperature: at 90°C for 8

h, Mp.136-138°C. 1H NMR(300 MHz, CDCl3): δ = 1.36 (t, 3H, J =

7.14Hz, CH3), 1.36 (t, 3H, J = 7.14 Hz, CH3), 4.38 (q, 2H, J = 7.14 Hz, CH2), 4.38 (q, 2H, J =

7.14 Hz, CH2), 7.78-7.80 (m, 2H, ArH), 8.27-8.29 (m, 2H, ArH), 8.56 (s, 2H, ArH). 13C NMR

(75.5 MHz, CDCl3): δ = 28.7 (2CH3), 61.4 (2OCH2), 126.6, 127.1 (2CH), 132.3, 133.6 (2C),

133.7 (2CH), 135.9 (2C), 165.1 (2CO), 180.7 (2CO). IR (KBr): v = 3072, 2957, 2926, 2856 (w),

1725 (s), 1627, 1666 (m), 1650, 1597 (w), 1462 (m), 1379, 1328 (w), 1272 (s), 1122, 1071 (m),

1039, 1017, 960, 862, 795, 768, 741, 704, 651, 610, 573, 553 (w) cm−1. GC-MS (EI, 70 eV): m/z

(%) : 352 ([M]+, 6), 307 (19), 279 (100), 235 (11). HRMS (EI, 70 eV): calcd for C20H16O6 [M]+:

352.09414; found: 352.09347.

Di-tert-butyl 9,10-dioxo-9,10-dihydroanthracene-2,3-dicarboxylate (28h): Starting with 26

(316 mg, 1.0 mmol), 4-tert-butylacrylate 27h (320 mg, 2.5 mmol),

Pd(OAc)2 (11 mg, 5 mol%), XPhos (48 mg, 10 mol%), 28h was

isolated as a yellowish solid (334 mg, 82%), reaction temperature: at

90°C for 8 h, Mp.172-174°C. 1H NMR (300 MHz, CDCl3): δ = 1.56

(s, 9H, 3CH3), 1.56 (s, 9H, 3CH3), 7.73-7.80 (m, 2H, ArH), 8.23-8.29 (m, 2H, ArH), 8.44 (s, 2H,

ArH). 13C NMR (75.5 MHz, CDCl3): δ = 28.2 (2CH3), 83.3 (2C), 127.5, 127.9 (2CH), 132.3,

133.4 (2C), 134.6 (2CH), 138.5 (2C), 165.3 (2CO), 181.9 (2CO). IR (KBr): v = 3075, 3002,

2978, 2924, 2853 (w), 1724 (m), 1713, 1679 (s), 1630, 1613 (w), 1590 (m), 1522, 1478, 1456,

1404 (w), 1391, 1367, 1340 (m), 1254, 1151, 1135, 1123 (s), 1042 (w), 1021, 961, 936 (m), 927

(w), 842, 792 (m), 776, 750, 741, 719 (w), 707 (s), 691 (m), 656, 641, 605 (w), 566 (m)

cm−1.GC-MS (EI, 70 eV): m/z (%) : 409 ([M+H]+, 31), 408 ([M]+, 100), 297 (20), 234 (23), 150

(13). HRMS (ESI, 70 eV): calcd for C24H24O6Na [M+Na]+: 431.14651; found: 431.14654.

2-(4-Chlorophenyl)anthracene-9,10-dione (29a): Starting with 26 (316 mg, 1.0 mmol), 4-

chlorostyrene 27a (346 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5

mol%), XPhos (48 mg, 10 mol%), 29a was isolated as a yellowish

solid (140 mg, 44%), reaction temperature: at 110°C for 8 h,

Mp.180-182°C. 1H NMR (300 MHz, CDCl3): δ = 7.06 (d, 2H, J =

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8.52 Hz, ArH), 7.21 (d, 2H, J = 8.52 Hz, ArH), 7.41 (d, 1H, J = 8.58 Hz, ArH ), 7.58 (d, 1H, J =

8.58 Hz, ArH ), 7.70-7.95 (m, 2H, ArH), 8.23 (s, 1H, ArH), 8.24-8.41 (m, 2H, ArH). 13C NMR

(75.5 MHz, CDCl3): δ = 125.4, 127.3, 128.6, 128.7, 129.4, 129.5, 130.9, 132.1 (CH), 132.5,

133.6, 134.1 (C), 134.3 (CH), 137.7, 145.0, 145.5 (C), 182.7, 183.1 (CO). IR (KBr): v = 3320,

3056, 3031, 2955, 2919, 2850 (w), 1671, 1587 (s), 1491, 1477 (m), 1455, 1419, 1390 (w), 1329,

1307, 1299, 1272, 1254 (s), 1210, 1184, 1174, 1157, 1127, 1106 (w), 1090 (s), 1045 (w), 1011

(s), 968 (w), 947, 931 (m), 906, 864 (w), 822 (s), 796 (m), 762, 748, 740 (w), 729 (m), 707 (s),

666, 644, 635 (m), 607, 586 (w), 562 (m), 534 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 319

([M+H]+, 22), 318 ([M]+, 100), 290 (18), 262 (12), 226 (33). HRMS (EI, 70 eV): calcd for

C20H11ClO2 [M]+: 318.04421; found: 318.04467.

2-(4-(Tert-butoxy)phenyl)anthracene-9,10-dione (29f): Starting with 26 (316 mg, 1.0 mmol),

4-tert-butoxystyrene 27f (440 mg, 2.5 mmol), Pd(OAc)2 (11

mg, 5 mol%), XPhos (48 mg, 10 mol%), 29f was isolated as a

yellowish solid (210 mg, 59%), reaction temperature: at 110°C

for 8 h, Mp.100-111°C. 1H NMR (300 MHz, CDCl3): δ =1.34

(s, 9H, 3CH3), 7.04 (d, 2H, J = 8.70 Hz, ArH), 7.56 (d, 2H, J = 8.70 Hz, ArH), 7.69-7.72 (m, 2H,

ArH), 7.89 (dd, 1H, J = 1.98, 8.13 Hz, ArH), 8.21-8.26 (m, 3H, ArH), 8.41 (d, 1H, J = 1.83 Hz,

ArH). 13C NMR (75.5 MHz, CDCl3): δ = 28.9 (CH3), 79.1(C), 124.3, 125.1, 127.1, 127.2, 127.9,

128.0 (CH), 131.7 (C), 131.9 (CH), 133.5, 133.6, 133.7, 133.9 (C), 134.0, 134.1 (CH), 146.4 (C),

156.6 (CO), 182.8, 183.3 (CO). IR (KBr): v = 3310, 3063, 3034, 2973, 2922, 2850 (w), 1673,

1589 (s), 1513 (m), 1480, 1456, 1425, 1388 (w), 1364, 1326, 1299, 1278, 1250, 1239 (m), 1156

(s), 1108, 1029, 1011, 971 (w), 954, 932 (m), 923 (w), 892 (s), 872 (w), 850 (s), 791 (w), 722

(m), 705 (s), 670, 636, 618, 569 (w), 535 (m) cm−1.GC-MS (EI, 70 eV): m/z (%) : 356 ([M]+,

20), 300 (100), 272 (17), 244 (14), 215 (21). HRMS (ESI, 70 eV): calcd for C24H20O3 [M]+:

356.14070; found: 356.14105.

Ethyl 9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (29g): Starting with 26 (316 mg, 1.0

mmol), ethylacrylate 27g (250 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5

mol%), XPhos (48 mg, 10 mol%), 29g was isolated as a yellowish

solid (104 mg, 37%+28g), reaction temperature: at 110°C for 8 h,

Mp.143-145°C. 1H NMR (300 MHz, CDCl3): δ = 1.38 (t, 3H, J =

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7.14 Hz, CH3), 4.39 (q, 2H, J = 7.14 Hz, CH2), 7.72-7.80 (m, 2H, ArH), 8.20-8.28 (m, 2H, ArH),

8.30 (s, 1H, ArH), 8.35 (dd, 1H, J = 1.68, 8.07 Hz, ArH), 8.84 (d, 1H, J = 1.29 Hz, ArH). 13C

NMR (62.9 MHz, CDCl3): δ = 30.9 (CH3), 61.9 (OCH2), 127.3, 127.4, 127.5, 128.5 (CH), 133.3,

133.4, 133.5 (C), 134.3, 134.4, 134.5 (CH), 135.5, 136.0 (C), 165.0 (CO), 182.3, 182.5 (CO). IR

(KBr): v = 3419, 3325, 3099, 3076, 3041, 2991, 2964, 2915, 2852 (w), 1717, 1674, 1588 (s),

1481, 1453, 1411, 1392, 1371 (w), 1330, 1316, 1292 (m), 1264, 1240 (s), 1162, 1108, 1083,

1025, 1015, 971, 928 (m), 908 (w), 869 (m), 818 (w), 797, 764 (m), 702 (s), 651 (w), 631 (m)

cm−1. GC-MS (EI, 70 eV): m/z (%) : 280 ([M]+, 34), 252 (49), 235 (100), 207 (26), 151 (41).

HRMS (EI, 70 eV): calcd for C17H12O4 [M]+: 280.07301; found: 280.07294.

Tert-butyl 9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (29h): Starting with 26 (316 mg,

1.0 mmol), 4-tert-butylacrylate 27h (320 mg, 2.5 mmol),

Pd(OAc)2 (11 mg, 5 mol%), XPhos (48 mg, 10 mol%), 29h was

isolated as a yellowish solid (184 mg, 60%+28h), reaction

temperature: at 110°C for 8 h, Mp.119-121°C. 1H NMR (300

MHz, CDCl3): δ = 1.57 (s, 9H, 3CH3), 7.71-7.77 (m, 2H, ArH), 8.19-8.30 (m, 4H, ArH), 8.76-

8.77 (m, 1H, ArH). 13C NMR (75.5 MHz, CDCl3): δ = 28.2 (CH3), 82.5 (C), 127.3, 127.4, 128.4

(CH), 133.4, 133.5 (C), 134.2, 134.4, 134.5 (CH), 135.7, 138.0 (C), 164.1 (CO), 182.4, 182.6

(CO). IR (KBr): v = 3410, 3327, 2996, 2976, 2923, 2874, 2853 (w), 1712, 1674 (s), 1590 (m),

1483, 1476, 1462, 1391 (w), 1368, 1332 (m), 1274, 1246 (s), 1183 (w), 1154 (s), 1124, 1093

(m), 1036, 977, 968 (w), 930 (m), 894 (w), 865, 846, 793 (m), 764, 751 (w), 700 (s), 634 (m)

cm−1.GC-MS (EI, 70 eV): m/z (%) : 308 ([M]+, 21), 253 (100), 235 (86), 208 (59), 151 (51).

HRMS (ESI, 70 eV): calcd for C19H16O4 [2M+Na]+: 639.19844; found: 639.19859.

Octadecyl 9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (29i): Starting with 26 (316 mg,

1.0 mmol), octadecylacrylate

27i (325 mg, 2.5 mmol),

Pd(OAc)2 (11 mg, 5 mol%),

XPhos (48 mg, 10 mol%),

29i was isolated as a yellowish solid (231 mg, 46%), reaction temperature: at 110°C for 8 h,

Mp.103-105°C.1H NMR (300 MHz, CDCl3): δ = 1.16-1.19 [m, 35H, 16(CH2)CH3], 4.32 (q, 2H,

J = 6.75 Hz, CH2), 7.73-7.75 (m, 2H, ArH), 8.21-8.29 (m, 2H, ArH), 8.30 (s, 1H, ArH), 8.35 (dd,

��

1H, J = 1.65, 8.10 Hz, ArH), 8.85 (d, 1H, J = 1.26 Hz, ArH).13C NMR (62.9 MHz, CDCl3):

δ = 14.1 (CH3), 22.7, 26.0, 28.6, 29.2, 29.3, 29.5, 29.6, 29.6, 29.7 (CH2), 66.1 (OCH2), 127.3,

127.4, 127.5, 128.5 (CH), 133.3, 133.4, 133.5 (C), 134.3, 134.4, 134.5 (CH), 135.6, 136.0 (C),

165.1 (CO), 182.3, 182.5 (CO). IR (KBr): v = 2958 (w), 2915, 2848, 1720, 1670 (m), 1606 (w),

1589, 1472 (m), 1406, 1392, 1365, 1332, 1326, 1300 (w), 1265, 1242 (s), 1165 (m), 1126, 1097,

1050, 1027, 1018, 995, 980 (w), 947 (m), 928, 906, 867, 843, 818 (w), 799 (m), 763, 751, 741

(w), 717 (m), 706 (s), 646, 634, 567, 540 (w) cm−1. GC-MS (EI, 70 eV): m/z (%) : 505 ([M+H]+,

30), 504 ([M]+, 100), 254 (69), 253 (30), 235 (12). HRMS (EI, 70 eV): calcd for C33H44O4 [M]+:

504.32341; found: 504.32231.

2-Methoxyethyl 9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (29j): Starting with 26

(316 mg, 1.0 mmol), ethylene glycol methyl ether acrylate

27j (325 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol%), XPhos

(48 mg, 10 mol%), 29j was isolated as a yellowish solid

(220 mg, 71%), reaction temperature: at 110°C for 8 h,

Mp.125°C. 1H NMR (300 MHz, CDCl3): δ = 3.38 (s, 3H, OCH3), 3.69-3.73 (m, 2H, CH2), 4.47-

4.50 (m, 2H, OCH2), 7.72-7.79 (m, 2H, ArH), 8.24-8.30 (m, 2H, ArH), 8.32 (brs, 1H, ArH), 8.38

(dd, 1H, J = 1.71, 8.10 Hz, ArH), 8.88-8.89 (m, 1H, ArH). 13C NMR (75.5 MHz, CDCl3):

δ = 59.1 (OCH3), 64.9 (CH2), 70.3 (OCH2), 127.4, 127.5, 127.5, 128.8 (CH), 133.4, 133.5, 133.6

(C), 134.4, 134.5, 134.7 (CH), 135.1, 136.1 (C), 165.1 (CO), 182.3, 182.6 (CO). IR (KBr): v

= 3428, 3326, 3099, 3079, 3046, 2960, 2925, 2889, 2850, 2828, 2815, 1999, 1871 (w), 1717,

1674 (s), 1588 (m), 1477, 1463, 1440, 1416, 1404, 1373 (w), 1330, 1294 (m), 1266, 1242 (s),

1204, 1162 (m), 1115, 1106 (s), 1077 (m), 1021 (s), 979, 966 (w), 930 (m), 880, 874 (w), 862

(m), 824 (w), 795 (m), 775, 764 (w), 700 (s), 650 (w), 635 (m), 541 (w) cm−1. GC-MS (EI,

70 eV): m/z (%) : 310 ([M]+, 21), 278 (11), 235 (100), 207 (25), 179 (8), 151 (60), 58 (58).

HRMS (EI, 70 eV): calcd for C18H14O5[M]+: 310.08358; found: 310.08340.

��

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��

X-ray Crystal Data

Data for compound 5b

Identification code dz-t16

Empirical formula C22H15F3O4S2

Formula weight 464.46

Temperature 173 (2) K

Wavelength 0.71073 Å

Crystal system Monoclinic

Space group (H.-M.) P21/c

Space group (Hall) -P 2ybc

Unit cell dimensions a = 5.2396 (2) Å = = 90.00°

b = 19.5582 (9) Å P = 96.074 (2)°

c = 19.2611 (8) Å Q = 90.00°

Volume 1962.74 (14) Å3

Z 4

Density (calculated) 1.572 Mg /m3

Absorption coefficient 0.33 mm−1

F (000) 952

Crystal size 0.99 × 0.18 × 0.05 mm3

R range for data collection 4.7–59.8°

Reflections collected 21304

Independent reflections 5620

Absorption correction multi-scan

Max. and Min. transmission 0.984 and 0.737

Refinement method full-matrix

Goodness-of-fit F2 1.046

Final R indices [I >2S (I)] R1 = 0.0393, wR2 = 0.0942

R indices (all data) R1 = 0.0646, wR2 = 0.1056

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Data for compound 5c










b = 30.3961 (18) Å P = 93.177 (4)°

c = 12.9846 (8) Å Q = 90.00°

Volume 2146.0 (2) Å3

Z 4



F (000) 1016

Crystal size 0.87 × 0.06 × 0.04 mm3










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Empirical formula C30H26O2S








b = 22.4121 (14) Å P = 91.156 (2)°

c = 17.7991 (11) Å Q = 90.00°

Volume 2267.5 (3) Å3

Z 4



F (000) 952

Crystal size 0.98 × 0.31 × 0.07 mm3










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Data for compound 10a

Identification code dz-ppa6





Crystal system Tetragonal

Space group (H.-M.) I 41/a

Space group (Hall) -I 4ad

Unit cell dimensions a = 29.1670 (5) Å = = 90 °

b = 29.1670 (5) Å P = 90 °

c = 9.5537 (2) Å Q = 90 °

Volume 8127.5 (3) Å3

Z 16



F (000) 3808

Crystal size 0.39 × 0.28 × 0.25 mm3










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Identification code dz-41

Empirical formula C16H7Br2F3O







Unit cell dimensions a = 13.3098 (6) Å = = 90.00 °

b = 14.9723 (7) Å P = 92.189 (3) °

c = 7.4196 (3) Å Q = 90.00 °

Volume 1477.49 (11) Å3

Z 4



F (000) 832

Crystal size 0.99 × 0.07 × 0.06 mm3










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Data for compound 16g

Identification code dz-62a

Empirical formula C21H11BrCl2O




Crystal system Triclinic, P

Space group (H.-M.) P -1

Space group (Hall) -P 1

Unit cell dimensions a = 5.9376 (2) Å = = 68.331 (2)°

b = 11.9185 (5) Å P = 80.137 (2)°

c = 13.6971 (5) Å Q = 82.890 (2)°

Volume 885.55 (6) Å3

Z 2



Crystal size 0.33 × 0.10 × 0.05 mm3










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Identification code dz-72b

Empirical formula C30H18F6O2




Crystal system Triclinic, P




b = 11.9138 (5) Å P = 96.065 (2)°

c = 14.8483 (6) Å Q = 92.612 (2)°

Volume 1180.62 (8) Å3

Z 2



F (000) 536

Crystal size 0.45 × 0.44 × 0.37 mm3










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Data for compound 23a

Identification code dz-tri-15R1a

Empirical formula C23H20BrNO2








b = 10.0572 (7) Å P = 97.808 (3)°

c = 26.376 (2) Å Q = 90.00°

Volume 3766.9 (5) Å3

Z 8



F (000) 1728

Crystal size 0.78 × 0.45 × 0.02 mm3










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Identification code dz-tri-10R2

Empirical formula C25H24BrN








b = 21.4854 (12) Å P = 100.020 (3)°

c = 7.3970 (5) Å Q = 90.00°

Volume 2047.2 (2) Å3

Z 4



F (000) 864

Crystal size 0.97 × 0.15 × 0.03 mm3










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Data for compound 28 c

Identification code dz-3b2

Empirical formula C34H32O2




Crystal system Triclinic




b = 15.173 (10) Å P = 99.729 (13)°

c = 15.251 (11) Å Q = 97.545 (16)°

Volume 2644 (3) Å3

Z 4

Density (calculated) 1.187 Mg/ m3


F (000) 1008

Crystal size 0.58 × 0.14 × 0.10 mm3

R range for data collection 6.5 - 59.1°









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Declaration/Erklärung

Here by I declare that this work has so far neither submitted to the Faculty of Mathematics and

Natural Sciences at the University of Rostock nor to any other scientific Institution for the

purpose of doctorate. Further more, I declare that I have written this work by myself and that I

have not used any other sources, other than mentioned earlier in this work.

Hiermit erkläre ich, daß diese Arbeit bisher von mir weder an der Mathematisch-

Naturwissenschaftlichen Fakultät der Universität Rostock noch an einer anderen

wissenschaftlichen Einrichtung zum Zwecke der Promotion eingereicht wurde.

Ferner erkläre ich, dass ich diese Arbeit selbständig verfasst und keine anderen als die darin

angegebenen Hilfsmittel benutzt habe.

I hereby apply irrevocably to take oral examination in the form of a private viva voce and a

public presentation.�

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